Iron Absorption in Rats Increased by Yeast Glucan

The effects of brewer's yeast cell walls and two of its components, glucan and mannan, on the absorption of ⁵⁹Fe by anemic rats were investigated. After administration of the label, the percentage of ⁵⁹Fe taken up into the blood of group given glucan was generally similar to that of a group given yeast cell walls, both values were higher than in controls. The incorporation of ⁵⁹Fe into the small intestines was higher in the group given glucan than in the controls or a group given a glucan—mannan mixture. Glucan is the main substance in yeast cell walls that increases iron absorption.     

The Effects of Physical Exercise on the Serum Iron Profile in Spontaneously Hypertensive Rats

The purpose of this study was to evaluate the profile of serum iron in spontaneously hypertensive rats after an aerobic physical exercise. To accomplish this, 12 normotensive Wistar rats and 12 spontaneously hypertensive rats were distributed into “physical exercise” and “no physical exercise” groups. The animals in the physical exercise group underwent to an aerobic exercise for a total of 4 weeks. Blood was collected for the analysis of iron. Our results indicate that rats of the physical exercise group had significantly lower serum iron levels after the aerobic exercise protocol compared to the spontaneously hypertensive rats no physical exercise group (F _(3,16) = 4.4915, p < 0.01). No significant difference was found between no physical exercise groups. The results indicated that the difference in iron may be due to an increased demand for iron, prompted by chronic physical exercise. In addition, erythrocytosis has been associated with increased blood pressure in spontaneously hypertensive rats, suggesting that iron reduction may be related to decreased blood pressure in these animals.     

Renal Function in Analgesic Nephropathy

Comprehensive one-day renal function tests in 20 patients with a history of analgesic abuse showed varying degrees of chronic renal failure in all. There was no evidence of a selective defect in proximal tubular function, while a defective concentrating mechanism, usually considered necessary for the diagnosis of analgesic-induced renal damage, could be demonstrated in only 16 patients. A urinary acidification defect associated with a concentrating defect was found in nine cases and was thought to reflect specific collecting duct dysfunction. Urinary ammonium excretion was reduced in 13 subjects, owing to a reduced number of functioning nephrons or inadequate acidification, or both. Low citrate excretion was frequently encountered, and this, as well as defective urinary acidification, may play some part in predisposing patients with analgesic nephropathy to intrarenal calcification and progressive renal failure.     

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm.     

Paeoniflorin Prevents Diabetic Nephropathy in Rats

The aim of this study was to test the hypothesis that paeoniflorin prevents the progression of diabetic nephropathy by modulating the inflammatory process. Sprague–Dawley rats were divided into 5 groups: nondiabetic control rats; untreated diabetic model (DM) rats; and DM rats treated with 5, 10, or 20 mg/kg paeoniflorin in drinking water once daily. Rats received a single intravenous injection of streptozotocin to induce diabetes; 9 wk after injection, rats began the 8-wk daily paeoniflorin treatment regimen. Compared with that of nonDM controls, the urinary albumin:creatinine ratio was increased significantly in untreated DM rats; this ratio was decreased in DM rats treated with 5, 10, or 20 mg/kg paeoniflorin compared with that of untreated DM rats. In addition, paeoniflorin treatment effectively suppressed glomerular hypertrophy; blood glucose; the expression of transforming growth factor β, type IV collagen, and intercellular adhesion molecule 1; and renal infiltration of macrophages compared with levels in untreated DM rats. Furthermore, renal nuclear factor κB activity was increased in untreated but not paeoniflorin-treated DM rats. In conclusion, our data suggest that the preventive effects of paeoniflorin may be mediated by its antiinflammatory actions.Abbreviations: DM, diabetic model; ECM, extracellular matrix; ICAM1, intercellular adhesion molecule 1; MCP1, monocyte chemoattractant protein 1; NFκB, nuclear factor κB; TGFβ, transforming growth factor βDiabetic nephropathy is the most common cause of endstage renal disease and high mortality in humans. Adequate control of blood glucose may slow the rate of its progression, but it is still difficult to achieve strict glycemic control for diabetic patients in the longer term, due at least in part to the limitations of available therapeutic approaches.³ Recent studies have suggested the emerging role of inflammatory processes in the pathogenesis of diabetic nephropathy in addition to other well-known mechanisms.In human renal disease, transforming growth factor β (TGFβ) may mediate the buildup of tissue extracellular matrix (ECM) proteins.¹⁷ This cytokine reportedly stimulated ECM protein accumulation in diabetic tissues by upregulating the production of ECM proteins or by downregulating the production of ECM-degrading enzymes.²⁶ Renal levels of TGFβ1 increase in both experimental and human diabetes. In addition, TGFβ1 induces the synthesis of ECM components including collagen types I, III, and IV and fibronectin.^2,5Intercellular adhesion molecule 1 (ICAM1) is a key adhesion molecules. In addition, the ICAM1-dependent infiltration of macrophages into the kidney is very important in the pathogenesis of diabetic nephropathy.¹⁸ In addition, the expression of ICAM1 is rapidly induced and maintained for a long time in renal tissues after induction of diabetes in experimental type 1 diabetic rats.^14,20 Macrophage infiltration was blocked by antiICAM1 antibody, confirming that ICAM1 mediates macrophage infiltration into the diabetic kidney.⁶ Furthermore, ICAM1-deficient mice were protected from renal injury after the induction of diabetes, suggesting that the inflammatory process is a critical factor for the development of diabetic nephropathy.²¹Despite the availability of treatments that lower blood glucose and blood pressure, many diabetic patients are still prone to developing kidney failure, which no currently available therapies can reverse.²⁴ Therefore a search is needed for new therapeutic approaches—based on novel mechanisms of action—to the treatment of diabetic nephropathy. Paeoniflorin is a monoterpene glucoside and a component of the total glucoside extract obtained from the root of Paeonia lactiflora.²⁸ This extract was approved for marketing in China in 1998.²³ As a disease-modifying drug, the total glucoside extract of peony has both antiinflammatory and immune-regulatory effects and is used in the treatment of rheumatoid arthritis, hepatitis, systemic lupus erythematosus, and mesenteric hyperplastic nephritis.^8,9,27 The goal of this study is to address whether paeoniflorin might prevent the progression of diabetic nephropathy through the inhibition of the inflammatory processes including TGFβ, type IV collagens, and ICAM1 expression, monocyte chemoattractant protein 1 (MCP1), nuclear factor κB (NFκB) activation, and macrophage infiltration.     

Increased Expression of the Very Low-Density Lipoprotein Receptor Mediates Lipid Accumulation in Clear-Cell Renal Cell Carcinoma

Clear-cell renal cell carcinoma (RCC) is, in most cases, caused by loss of function of the tumor suppressor gene von Hippel–Lindau, resulting in constitutive activation of hypoxia-inducible factor (HIF)-1α and expression of hypoxia-induced genes in normoxic conditions. Clear-cell RCC cells are characterized histologically by accumulation of cholesterol, mainly in its ester form. The origin of the increased cholesterol remains unclear, but it is likely explained by an HIF-1α-driven imbalance between cholesterol uptake and excretion. Here, we showed that expression of the very low-density lipoprotein receptor (VLDL-R) was significantly increased in clear-cell RCC human biopsies compared with normal kidney tissue. Partial knockdown of HIF-1α in clear-cell RCC cells significantly reduced the VLDL-R expression, and knockdown of either HIF-1α or VLDL-R reduced the increased lipid accumulation observed in these cells. We also showed increased uptake of fluorescently labeled lipoproteins in clear-cell RCC cells, which was significantly reduced by knockdown of HIF-1α or VLDL-R. Taken together, our results support the concept that the pathological increase of HIF-1α in clear-cell RCC cells upregulates VLDL-R, which mediates increased uptake and accumulation of lipids. These results explain the morphological characteristics of clear-cell RCC, and open up novel possibilities for detection and treatment of clear-cell RCC.     

Chronic Treatment with Atrial Natriuretic Peptide in Spontaneously Hypertensive Rats: Beneficial Renal Effects and Sex Differences

Objective

The aim of this study was to investigate the effects of chronic treatment with atrial natriuretic peptide (ANP) on renal function, nitric oxide (NO) system, oxidative stress, collagen content and apoptosis in kidneys of spontaneously hypertensive rats (SHR), as well as sex-related differences in the response to the treatment.

Methods

10 week-old male and female SHR were infused with ANP (100 ng/h/rat) or saline (NaCl 0.9%) for 14 days (subcutaneous osmotic pumps). Systolic blood pressure (SBP) was recorded and diuresis and natriuresis were determined. After treatment, renal NO synthase (NOS) activity and eNOS expression were evaluated. Thiobarbituric acid-reactive substances (TBARS), glutathione concentration and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were determined in the kidney. Collagen was identified in renal slices by Sirius red staining and apoptosis by Tunel assay.

Results

Female SHR showed lower SBP, oxidative stress, collagen content and apoptosis in kidney, and higher renal NOS activity and eNOS protein content, than males. ANP lowered SBP, increased diuresis, natriuresis, renal NOS activity and eNOS expression in both sexes. Renal response to ANP was more marked in females than in males. In kidney, ANP reduced TBARS, renal collagen content and apoptosis, and increased glutathione concentration and activity of GPx and SOD enzymes in both sexes.

Conclusions

Female SHR exhibited less organ damage than males. Chronic ANP treatment would ameliorate hypertension and end-organ damage in the kidney by reducing oxidative stress, increasing NO-system activity, and diminishing collagen content and apoptosis, in both sexes.     

Nitric Oxide Synthase in Spontaneously Hypertensive Rats

Since its discovery by Furchgott and Zawadzki in 1980 [18], endothelium-derived relaxing factor (EDRF) has been shown to play a central role in the cardiovascular system [10]. The endothelial product is chemically equivalent to nitric oxide (NO) [23, 40] or a biochemical congener thereof [48]. Fifteen years ago, this small, simple and highly toxic molecule was known as a lengthy list of environmental pollutants found in unsavory haunts such as smoke and smog, and even as destroyer of ozone, suspected carcinogen, and precursor of acid rain. In addition, NO seems an unlikely biological jack of all trades for most of the body's functions are regulated by extraordinarily large and complex proteins and compounds. But over the past decade, diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body.     

Renalase Protects against Contrast-Induced Nephropathy in Sprague-Dawley Rats

Background

Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure. Oxidative stress, apoptosis and inflammation play crucial roles in CIN. Renalase is a newly discovered monoamine oxidase from the kidney. We hypothesize that renalase could protect against CIN through anti-oxidation, anti-inflammation and anti-apoptosis pathways.

Methods

We tested our hypothesis in vivo with a rat model of Ioversol-induced CIN and in vitro. Sprague-Dawley rats were divided into 4 groups (n = 6 per group): control group, Ioversol group (rats subjected to Ioversol-induced CIN), Ioversol plus vehicle group (CIN rats pretreated with vehicle) and Ioversol plus renalase group (CIN rats pretreated with 2 mg/kg recombinant renalase). HK2 cells were treated with Ioversol or H₂O₂.

Results

The results showed that pretreatment with renalase attenuated the deterioration of renal function, tubular necrosis, oxidative stress, apoptosis and inflammation (P<0.05). Furthermore, renalase protected HK2 cells against the cytotoxicity of Ioversol and suppressed Caspase-3 activity, oxidative stress and apoptosis induced by H₂O₂.

Conclusion

Recombinant renalase protected CIN in rats through anti-oxidation, anti-apoptosis and anti-inflammation mechanisms.     

Outcomes of Renal Transplantation in HIV-1 Associated Nephropathy

Introduction

Several studies have demonstrated that renal transplantation in HIV positive patients is both safe and effective. However, none of these studies have specifically examined outcomes in patients with HIV-associated nephropathy (HIVAN).

Methods

Medical records of all HIV-infected patients who underwent kidney transplantation at Johns Hopkins Hospital between September 2006 and January 2014 were reviewed. Data was collected to examine baseline characteristics and outcomes of transplant recipients with HIVAN defined pathologically as collapsing focal segmental glomerulosclerosis (FSGS) with tubulo-interstitial disease.

Results and Discussion

During the study period, a total of 16 patients with HIV infection underwent renal transplantation. Of those, 11 patients were identified to have biopsy-proven HIVAN as the primary cause of their end stage renal disease (ESRD) and were included in this study. They were predominantly African American males with a mean age of 47.6 years. Seven (64%) patients developed delayed graft function (DGF), and 6 (54%) patients required post-operative dialysis within one week of transplant. Graft survival rates at 1 and 3 years were 100% and 81%, respectively. Acute rejection rates at 1 and 3 years were 18% and 27%, respectively. During a mean follow up of 3.4 years, one patient died.

Conclusions

Acute rejection rates in HIVAN patients in this study are higher than reported in the general ESRD population, which is similar to findings from prior studies of patients with HIV infection and ESRD of various causes. The high rejection rates appear to have no impact on short or intermediate term graft survival.     

Renal Function and Hematology in Rats with Congenital Renal Hypoplasia

Renal hypoplasia due to a congenitally reduced number of nephrons progresses to chronic kidney disease and may cause renal anemia, given that the kidneys are a major source of erythropoietin in adults. Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and develop CKD. This study assessed the renal function and hematologic changes in HPK rats from 70 to 210 d of age. HPK rats demonstrated deterioration of renal excretory function, slightly macrocytic erythropenia at all days examined, age-related increases in splenic hemosiderosis accompanied by a tendency toward increased hemolysis, normal plasma erythropoietin levels associated with increased hepatic and decreased renal erythropoietin production, and maintenance of the response for erythropoietin production to hypoxic conditions, with increased interstitial fibrosis at 140 d of age. These results indicate that increases in splenic hemosiderosis and the membrane fragility of RBC might be associated with erythropenia and that hepatic production of erythropoietin might contribute to maintaining the blood Hgb concentration in HPK rats.Abbreviations: CKD, chronic kidney disease; HGN, hypogonadism; HPK, hypoplastic kidneyApproximately 10% to 13% of the general population has chronic kidney disease (CKD), including an estimated 13.3 million people in Japan.^13,15,20 Moreover, more than 1.1 million patients worldwide require maintenance dialysis, and that number continues to increase.²⁴ Determining the pathogenesis of CKD, identifying clinical makers of early stages of CKD, and developing effective methods to treat CKD are required, especially given that CKD has been reported to be a risk factor for cardiovascular disease, with high mortality rates.^11,13,15 Patients with CKD are frequently anemic, due to a low level of erythropoietin and inhibition of erythropoiesis.^12,27 The decreased production of erythropoietin may result from the transdifferentiation of interstitial fibroblasts to myofibroblasts, resulting in increased production of extracellular matrix in the kidneys.^4,29 The number of nephrons in the kidneys at birth varies greatly,^5,19 and a congenital reduction in number of nephrons is thought to be related to the occurrence and prognosis of CKD.^9,17,18,21 Therefore, a CKD animal model with a reduced number of nephrons is useful for studying the pathophysiology of and treatments for CKD.Affected rats in the hypogonadism (HGN) inbred strain are characterized by male sterility due to hypogonadism,^37,41 reduced female fertility due to ovarian hypoplasia,^30,31 and progressive renal dysfunction due to bilateral hypoplastic kidneys (HPK).^32,33 These defects are controlled by a single autosomal recessive gene, hgn.^38,40 Linkage analysis and sequencing of candidate genes revealed a 25-bp duplicated insertion mutation in exon 7 of Astrin/Spag5, which encodes a microtubule-associated protein.³⁹ Because this mutation causes a premature terminal codon resulting in a truncated Astrin protein that lacks the primary spindle-targeting domain, the cause of the phenotype is considered to be a loss-of-function type mutation of the Astrin gene.^38,39 The recovery of normal fertility and renal function in homozygous mutant rats by a transgene comprising normal Astrin cDNA indicates that Astrin is required for normal testicular and renal development.²²The HGN strain was isolated from the sixth filial generation of a polygenic hydronephrotic rat strain derived from the original stock of the Wistar–Imamichi rat closed colony.⁴¹ Because the occurrence of hydronephrosis would influence renal development and function, we established another hypogonadism strain (HGN II) that was directly derived from the original closed colony.³⁶ The HGN II strain has been maintained by inbreeding between carriers, and the mutated gene responsible for the phenotype in the HGN II strain is identical to that in the HGN strain.³⁹ The affected rats of the HGN II strain show a similar phenotype as that of the HGN strain with regard to hypogonadism and HPK.^35,36Although male HPK rats in the HGN and HGN II strains have only about 20% of the nephrons present in normal kidney, the total glomerular filtration rate per kidney is compensated by hyperfiltration of individual glomeruli.^32,36 However, continuous glomerular hyperfiltration and functional overload of individual nephrons can result in a deterioration in renal excretion. Histologically, HPK rats demonstrate glomerular hypertrophy and dilation of the renal tubules.^32,36 As these rats age, cast formation in tubular lumen, glomerular sclerosis, and cellular infiltration into interstitial tissue occur.^33,35 In addition, age-related features of renal deterioration, including polyposia, polyuria, azotemia, albuminuria, and hypertension, follow,³⁵ and secondary hyperparathyroidism, osteodystrophy, and anemia emerge at advanced age in HPK rats.³³ Therefore HPK rats are a model for studying how a congenitally reduced nephron mass may induce CKD and secondary renal diseases, and HPK rats might be useful for identifying biomarkers related to these diseases. Because our previous studies in HPK rats^33,35 provided only limited information about the progression of CKD and renal anemia, the current study was designed to analyze multiple parameters related to renal function and hematology and to characterize the anemic tendencies in 70- to 210-d-old HPK rats. We found that the hematologic condition of HPK rats is characterized by reduced renal excretive function, erythropenia, increased hemolysis in the spleen, progressive renal fibrosis, and maintenance of normal plasma erythropoietin concentrations.     

Proteomic Response to Acupuncture Treatment in Spontaneously Hypertensive Rats

Previous animal and clinical studies have shown that acupuncture is an effective alternative treatment in the management of hypertension, but the mechanism is unclear. This study investigated the proteomic response in the nervous system to treatment at the Taichong (LR3) acupoint in spontaneously hypertensive rats (SHRs). Unanesthetized rats were subject to 5-min daily acupuncture treatment for 7 days. Blood pressure was monitored over 7 days. After euthanasia on the 7^th day, rat medullas were dissected, homogenized, and subject to 2D gel electrophoresis and MALDI-TOF analysis. The results indicate that blood pressure stabilized after the 5th day of acupuncture, and compared with non-acupoint treatment, Taichong-acupunctured rat’s systolic pressure was reduced significantly (P<0.01), though not enough to bring blood pressure down to normal levels. The different treatment groups also showed differential protein expression: the 2D images revealed 571±15 proteins in normal SD rats’ medulla, 576±31 proteins in SHR’s medulla, 597±44 proteins in medulla of SHR after acupuncturing Taichong, and 616±18 proteins in medulla of SHR after acupuncturing non-acupoint. In the medulla of Taichong group, compared with non-acupoint group, seven proteins were down-regulated: heat shock protein-90, synapsin-1, pyruvate kinase isozyme, NAD-dependent deacetylase sirtuin-2, protein kinase C inhibitor protein 1, ubiquitin hydrolase isozyme L1, and myelin basic protein. Six proteins were up-regulated: glutamate dehydrogenase 1, aldehyde dehydrogenase 2, glutathione S-transferase M5, Rho GDP dissociation inhibitor 1, DJ-1 protein and superoxide dismutase. The altered expression of several proteins by acupuncture has been confirmed by ELISA, Western blot and qRT-PCR assays. The results indicate an increase in antioxidant enzymes in the medulla of the SHRs subject to acupuncture, which may provide partial explanation for the antihypertensive effect of acupuncture. Further studies are warranted to investigate the role of oxidative stress modulation by acupuncture in the treatment of hypertension.     

Heterogeneity in Arterial Remodeling among Sublines of Spontaneously Hypertensive Rats

Objectives

Spontaneously hypertensive rats (SHR) have been used frequently as a model for human essential hypertension. However, both the SHR and its normotensive control, the Wistar Kyoto rat (WKY), consist of genetically different sublines. We tested the hypothesis that the pathophysiology of vascular remodeling in hypertension differs among rat sublines.

Methods and Results

We studied mesenteric resistance arteries of WKY and SHR from three different sources, at 6 weeks and 5 months of age. Sublines of WKY and SHR showed differences in blood pressure, body weight, vascular remodeling, endothelial function, and vessel ultrastructure. Common features in small mesenteric arteries from SHR were an increase in wall thickness, wall-to-lumen ratio, and internal elastic lamina thickness.

Conclusions

Endothelial dysfunction, vascular stiffening, and inward remodeling of small mesenteric arteries are not common features of hypertension, but are subline-dependent. Differences in genetic background associate with different types of vascular remodeling in hypertensive rats.     

The Heme Oxygenase System Suppresses Perirenal Visceral Adiposity,Abates Renal Inflammation and Ameliorates Diabetic Nephropathy in Zucker Diabetic Fatty Rats

The growing incidence of chronic kidney disease remains a global health problem. Obesity is a major risk factor for type-2 diabetes and renal impairment. Perirenal adiposity, by virtue of its anatomical proximity to the kidneys may cause kidney disease through paracrine mechanisms that include increased production of inflammatory cytokines. Although heme-oxygenase (HO) is cytoprotective, its effects on perirenal adiposity and diabetic nephropathy in Zucker-diabetic fatty rats (ZDFs) remains largely unclear. Upregulating the HO-system with hemin normalised glycemia, reduced perirenal adiposity and suppressed several pro-inflammatory/oxidative mediators in perirenal fat including macrophage-inflammatory-protein-1α (MIP-1α), endothelin (ET-1), 8-isoprostane, TNF-α, IL-6 and IL-1β. Furthermore, hemin reduced ED1, a marker of pro-inflammatory macrophage-M1-phenotype, but interestingly, enhanced markers associated with anti-inflammatory M2-phenotype such as ED2, CD206 and IL-10, suggesting that hemin selectively modulates macrophage polarization towards the anti-inflammatory M2-phenotype. These effects were accompanied by increased adiponectin, HO-1, HO-activity, atrial-natriuretic peptide (ANP), and its surrogate marker, urinary-cGMP. Furthermore, hemin reduced renal histological lesions and abated pro-fibrotic/extracellular-matrix proteins like collagen and fibronectin that deplete nephrin, an important transmembrane protein which forms the scaffolding of the podocyte slit-diaphragm allowing ions to filter but not massive excretion of proteins, hence proteinuria. Correspondingly, hemin increased nephrin expression in ZDFs, reduced markers of renal damage including, albuminuria/proteinuria, but increased creatinine-clearance, suggesting improved renal function. Conversely, the HO-blocker, stannous-mesoporphyrin nullified the hemin effects, aggravating glucose metabolism, and exacerbating renal injury and function. The hemin effects were less-pronounced in Zucker-lean controls with healthy status, suggesting greater selectivity of HO in ZDFs with disease. We conclude that the concomitant reduction of pro-inflammatory/oxidative mediators, macrophage infiltration and profibrotic/extracellular-matrix proteins, coupled to increased nephrin, adiponectin, ANP, cGMP and creatinine clearance may account for improved renal function in hemin-treated ZDFs. These findings suggest that HO-inducers like hemin may be explored against the co-morbidity of perirenal adiposity and diabetic nephropathy.     

树突状细胞C型凝集素DC-SIGN在人肾炎组织和肾小管上皮细胞表达

DC-SIGN(DC-specificICAM-grabbingnon-integrin,亦称CD209)属树突状细胞(DC)表面C型凝集素的膜蛋白。作为DC黏附及模式识别受体,其参与介导了DC的炎症组织迁移,识别捕获病原微生物,以及随后激活静息T细胞启动的免疫应答。为此观察了DC-SIGN及DC-SIGN DC在肾炎患者肾组织中表达和分布,以及DC-SIGN在炎性状态下培养人肾小管上皮细胞表达,探讨与肾小管间质炎症病变和损伤的关系。结果显示,DC-SIGN在正常肾组织基本不表达,而在肾炎早期即以肾小管上皮细胞为主表达上调,且随肾小管间质病变程度加重表达增强(P<0.01),与肾小管间质病变程度明显相关(P<0.01)。此外,DC-SIGN在经TNF-α刺激炎性状态下的人肾小管上皮细胞也明显表达。进一步发现,DC-SIGN DC在肾炎早期以肾间质为主分布聚集,也随肾小管间质病变程度加重明显增多(P<0.01),与肾小管间质病变程度显著相关(P<0.01),也与DC-SIGN表达相关联(P<0.01)。另外,DC-SIGN DC在肾小管间质分布数量与肾炎患者肾功能改变明显相关(P<0.05)。研究结果提示,DC-SIGN也是肾小管间质早期炎症的启动参与因素,其介导DC可能也参与了人肾炎肾小管间质的免疫损伤机制。     

C肽对糖尿病大鼠肾脏的影响

比较C肽和胰岛素对大鼠糖尿病肾病的治疗作用。方法:选取Wistar大鼠40只,分为正常对照组(NG组)和糖尿病组(DM组),糖尿病组链脲佐菌素诱发大鼠成模后,随机分为三组:糖尿病组(DM组)、胰岛素组(IG组)和C肽组(ICG组)。治疗8周后测定各组大鼠24小时尿白蛋白排泄率(UAER)、肾重/体重,并观察糖尿病大鼠肾脏超微结构变化。结果:24小时尿白蛋白排泄率:糖尿病组明显增加,C肽组明显低于糖尿病组和胰岛素组,差异具有显著性。大鼠肾脏超微结构变化:各组大鼠肾小球截面积、肾小球平均体积(MGV)、细胞外基质/肾小球截面积比值、细胞外基质截面积、肾小球基底膜厚度相比,糖尿病组明显升高,C肽组较胰岛素组和糖尿病组明显下降,差异具有显著性。结论:C肽治疗可以降低24小时尿白蛋白排泄率,改善糖尿病大鼠肾脏超微结构病变。     

Egg-Derived Tri-Peptide IRW Exerts Antihypertensive Effects in Spontaneously Hypertensive Rats

Background

There is a growing interest in using functional food components as therapy for cardiovascular diseases such as hypertension. We have previously characterized a tri-peptide IRW (Ile-Arg-Trp) from egg white protein ovotransferrin; this peptide showed anti-inflammatory, anti-oxidant and angiotensin converting enzyme (ACE) inhibitor properties in vitro. Given the pathogenic roles played by angiotensin, oxidative stress and inflammation in the spontaneously hypertensive rat (SHR), we tested the therapeutic potential of IRW in this well-established model of hypertension.

Methods and Results

16–17 week old male SHRs were orally administered IRW at either a low dose (3 mg/Kg BW) or a high dose (15 mg/Kg BW) daily for 18 days. Blood pressure (BP) and heart rate were measured by telemetry. Animals were sacrificed at the end of the treatment for vascular function studies and measuring markers of inflammation. IRW treatment attenuated mean BP by ~10 mmHg and ~40 mmHg at the low- and high-dose groups respectively compared to untreated SHRs. Heart rate was not affected. Reduction in BP was accompanied by the restoration of diurnal variations in BP, preservation of nitric oxide dependent vasorelaxation, as well as reduction of plasma angiotensin II, other inflammatory markers and tissue fibrosis.

Conclusion

Our results demonstrate anti-hypertensive effects of IRW in vivo likely mediated through ACE inhibition, endothelial nitric oxide synthase and anti-inflammatory properties.