Azafluorenones from Oxandra cf. major and biogenetic considerations

The stem bark of Oxandra cf. major, which contains large amounts of 7,7′-bisdehydroaporphine alkaloids, has also yielded three commonplace steroids, reticuline, four known aporphinoids and the new azafluorenones darienine, macondine and ursuline. Three biogenetic hypotheses are discussed in the light of the structures of the azafluorenones found to date in the Annonaceae.     

New azafluorenones with cytotoxic and carbonic anhydrase inhibitory properties: 2-Aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones

New azafluorenones, 2-aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones, were prepared to evaluate their cytotoxic/anticancer properties, also their inhibitory effects on hCA I and II isoenzymes. Aryl part was changed as [phenyl (H1), 4-methylphenyl (H2), 4-methoxyphenyl (H3), 4-fluorophenyl (H4), 4-bromophenyl (H5), 4-chlorophenyl (H6), 3-hydroxyphenyl (H7), and 4-hydroxyphenyl (H8)]. The structure of the synthesized compounds was characterized by ¹H NMR, ¹³C NMR and HRMS spectra.Cytotoxicity results of the series pointed out that the compounds H6 (PSE: 28.0) and H5 (PSE: 27.3), with the highest potency selectivity expression (PSE) value, can be considered as leader compounds of the study in designing novel anticancer agents. Additionally, all azafluorenones synthesized showed a good inhibition profile towards hCA I and II isoenzymes in the range of 54.14–73.72 nM and 67.28–76.15 nM, respectively.The compounds H5 and H6 can be considered for further designs with their cytotoxic and CA inhibitory profiles.     

冠状动脉内放射抑制球囊扩张术后ERK1/2活性及c-fos基因表达

本文旨在观察血管内放射对冠状动脉球囊扩张术后细胞外信号调节激酶１／２（ＥＲＫ１／２）及ｃ－ｆｏｓ基因表达的影响。实验对猪的左冠状动脉前降支或回旋支行球囊行过度扩张术,术后即刻能过血管内放射治疗系统对猪冠状动脉损伤局部给予２０Ｇｙ的放射剂量,分别是在术后３ｄ和３０ｄ处死动物,留取目标血管组织。通过反转录－聚合酶链反应定量检测血管内入射对球囊扩张术后血管组织ｃ－ｆｏｓ ｍＲＮＡ的表达,采用生化方法测定     

Urinary cholinesterase activity is increased in insulin-dependent diabetics: further evidence of diabetic tubular dysfunction.

We measured the cholinesterase activity in morning urines from 63 insulin-dependent diabetics and 27 controls. The total esterase (TotE) activity (Ellman's method) has been divided into aliesterase (AliE), pseudocholinesterase and acetylcholinesterase by means of two inhibitors, eserine and quinidine. Diabetics were divided in 2 groups according to the urinary albumin/creatinine ratio (mg/mmol, < 2 in group 1, > 2 in group 2). The urinary cholinesterase behavior was correlated with that of a known tubular lysosomal hydrolase, N-acetyl-beta-D-glucosaminidase (NAG). Compared to normals, in addition to a significant increase in urinary NAG in diabetes (in group 2 more than in group 1), TotE and AliE were also significantly raised (+36% and 109% of the controls, in group 1 as much as in group 2).     

β-Caryophyllene Attenuates Focal Cerebral Ischemia-Reperfusion Injury by Nrf2/HO-1 Pathway in Rats

This study aimed to identify the effect of β-caryophyllene (BCP) pretreatment and elucidate the Nrf2/HO-1 signaling mechanism after focal cerebral ischemia-reperfusion (I-R) injury in rats. Adult male Sprague–Dawley rats were randomly assigned to the sham-operated group, I-R group and BCP pretreated I-R group. At 24 h after reperfusion, neurological deficits and infarct volume were evaluated. Pathological changes of neuron in hippocampuses were observed by Nissil staining and transmission electron microscopy (TEM). Oxidative stress was assessed by malondialdehyde (MDA) level, lipid peroxidation (LPO), nitric oxide (NO), superoxide dismutase (SOD) and Catalase (CAT) activity. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were analysed by Western blotting and real-time quantitative polymerase chain reaction (Q-PCR). The protein expression of Bcl-2 and Bax was determined by immunohistochemistry. Apoptotic cells were detected using TUNEL staining. In I-R group, neurological deficit scores, cerebral infarct volume, MDA levels, LPO content, NO level, expression of Bax and TUNEL-positive cells were found to be increased at 24 h after I-R injury, while SOD activity, CAT activity and expression of Bcl-2 were decreased. However, results in the BCP pretreatment groups were reversed. And the protein and mRNA expressions of Nrf2 and HO-1 were significantly up-regulated in the BCP pretreated I-R group. Results of Nissil staining and TEM scan manifested that BCP remarkablely improved neuronal injury after I-R in rats. All the above suggested that BCP pretreatment played a neuroprotective role in cerebral I-R injury, which might be exerted by upregulating the expression of Nrf2 and HO-1 to ameliorate oxidative damage and neuronal apoptosis.     

COMP-Angiopoietin1 Potentiates the Effects of Bone Morphogenic Protein-2 on Ischemic Necrosis of the Femoral Head in Rats

Angiogenesis is considered essential for proper bone regeneration. The purpose of this investigation was to determine if a combined therapy of bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) can potentiate the therapeutic effect of BMP-2 in a rat model of ischemic necrosis of the femoral head (INFH). INFH was surgically induced in the femoral head of rats, and the animals were divided into the following groups: 1) a sham-operated group (sham group), 2) a bovine serum albumin-injected group (BSA group), 3) a BMP-2-injected group (BMP-2 group), and 4) a COMP-Ang1 and BMP-2-injected group (COMP-Ang1 + BMP-2 group) (n = 20/group). Radiologic, histologic, and histomorphometric assessments were performed to assess femoral head morphology, vascular density, and bone resorption activity. Western blots and immunohistochemical staining were performed to evaluate production of BMP-related signaling proteins in C3H10T1/2 cells and tissues. Real-time RT-PCR was performed to investigate expression of the target integrin gene, and the effect of integrin on C3H10T1/2 cells was determined using a cell adhesion assay. Radiographs obtained six weeks after injection revealed better preservation of the architecture of the femoral head in the COMP-Ang1 + BMP-2 group compared with the BSA and BMP-2 groups. Histological findings indicated increased trabecular bone and vascularity and decreased osteoclast bone resorption activity in the COMP-Ang1 + BMP-2 group compared with those in the BSA and BMP-2 groups. The combination of COMP-Ang1 and BMP-2 increased phosphorylation of Smad1/3/5, p38, and Akt. Increased integrin α3 and β1 mRNA expression in the COMP-Ang1 + BMP-2 group promoted cell adhesion. These results suggest that COMP-Ang1 preserved the necrotic femoral head through the potentiation of BMP-2 signaling pathways and angiogenesis. Combination treatment with COMP-Ang1 and BMP-2 may be a clinically useful therapeutic application in INFH.     

Impaired phagocytic activity of neutrophils in patients receiving haemodialysis: the critical role of iron overload.

The metabolic burst (as measured by the spontaneous and stimulated nitroblue tetrazolium tests), the phagocytosis of heat inactivated bakers'' yeast and of Staphylococcus aureus, the killing of Staph aureus, and the myeloperoxidase activity of polymorphonuclear neutrophils were studied in 11 patients receiving maintenance haemodialysis. Of these patients, six were polytransfused and had high serum ferritin concentrations (mean 5940 (SD 2925) micrograms/l; group 1), and five had normal serum ferritin values (mean 171 (116) micrograms/l; group 2). Patients in group 1 had a history of more infectious episodes (0.167 v 0.025 per patient per month) and significantly more genitourinary infections (p = 0.015) than those in group 2. Phagocytosis and myeloperoxidase activity were severely reduced in group 1 but normal in group 2. Percentages of neutrophils ingesting one or more particles together with the index of phagocytosis in patients'' serum were inversely correlated with serum ferritin concentrations. Four patients in group 1 were treated with desferrioxamine, and after six to 18 weeks of treatment phagocytosis and myeloperoxidase activity had returned to normal in three of them. These data suggest that in patients receiving haemodialysis iron overload due to multiple transfusions plays an important part in the mechanisms underlying the susceptibility to bacterial infections, mediated at least partially through impaired neutrophil function.     

Protective Effect of Zinc Aspartate on Long-Term Ischemia–Reperfusion Injury in Rat Skeletal Muscle

The present study investigated the protective effect of zinc aspartate, in connection with reactive oxygen species and nitric oxide, on long-term ischemia–reperfusion injury (IRI) in rat skeletal muscle. Following ketamine anesthesia, 24 rats were randomly assigned to four groups: groups 1 and 2, each without tourniquet application, received no drug and zinc, respectively; groups 3 and 4, each subjected to tourniquet-induced IRI (3 + 24 h), received no drug and zinc, respectively. IRI was achieved by the application of an elastic rubber band in the left hind limb of the anesthetized rats. Gastrocnemius muscle samples were obtained for biochemical measurements. Malondialdehyde levels were lower in group 2 and higher in group 3 than those seen in group 1. However, zinc aspartate (group 4) totally reversed malondialdehyde levels to control levels. Superoxide dismutase activity was increased in group 2 compared with group 1; however, there was no difference between groups 1 and 3, and Zn injection (group 4) increased superoxide dismutase activity. While catalase values were similar in groups 1 and 2, significant increments were observed in 3 and 4. A similar enhancement in glutathione levels were observed in groups 2 and 4 compared with group 1. Nitric oxide levels were lower in group 2 than 1, and no difference between groups 1 and 3 was demonstrated. In conclusion, zinc seems to be an effective treatment option against IRI.     

Ca^2+介导肾小管ICAM-1高表达参与肾结石的形成

本研究旨在探讨细胞间黏附分子1 (intercellular cell adhesion molecule-1, ICAM-1)在高钙尿肾结石(genetic hypercalcium renal stones, GHS)大鼠中的表达以及Ca^2+对肾小管上皮细胞ICAM-1的影响。取GHS大鼠和SD大鼠,荧光定量PCR检测肾组织ICAM-1 mRNA表达水平,免疫组化检测ICAM-1蛋白表达。比色法检测大鼠肾组织SOD活力和MDA水平。通过ICAM-1 siRNA转染大鼠肾小管上皮细胞系NRK-52E构建ICAM-1低表达细胞模型,Ca^2+(5 mmol/L)处理NRK-52E细胞,检测细胞SOD活力和MDA水平,通过Western blotting检测细胞ICAM-1蛋白表达水平。荧光定量PCR结果显示,与SD对照组相比,GHS组大鼠肾组织ICAM-1 mRNA水平显著升高,差异具有统计学意义(p<0.01);免疫组化结果显示,ICAM-1蛋白在GHS大鼠肾组织中呈阳性表达;氧化应激检测结果显示,与SD对照组比较,GHS组大鼠肾组织SOD活性显著降低,MDA含量显著升高,差异具有统计学意义(p<0.01)。Western blotting结果显示,与对照组比较,Ca^2+组NRK-52E细胞ICAM-1表达蛋白显著升高,差异具有统计学意义(p<0.01);与Ca^2+处理NC-siRNA组比较,Ca^2+处理ICAM-1 siRNA组NRK-52E细胞ICAM-1表达蛋白显著降低;与ICAM-1 siRNA组NRK-52E细胞比较,Ca^2+处理ICAM-1 siRNA组NRK-52E细胞后ICAM-1表达蛋白水平无显著性变化(p>0.05)。细胞氧化应激检测结果显示,与对照组比较,Ca^2+组NRK-52E细胞SOD活性显著降低,MDA含量显著升高,差异具有统计学意义(p<0.01);与Ca^2+处理NC-siRNA组比较,Ca^2+处理ICAM-1 siRNA组SOD活性显著升高,MDA含量显著降低,差异均具有统计学意义(p<0.01);与ICAM-1 siRNA组NRK-52E细胞比较,Ca^2+处理ICAM-1 siRNA组NRK-52E细胞SOD活力和MDA含量无显著性变化(p>0.05)。ICAM-1在GHS肾小管上皮细胞中高表达,Ca^2+诱导肾小管上皮细胞ICAM-1高表达,促进细胞氧化应激水平。     

饥饿再投喂对大鳞副泥鳅生长性能、肝脏抗氧化能力和肠道消化酶的影响

为探究周期性饥饿再投喂对大鳞副泥鳅(Paramisgurnus dabryanus)生长性能、抗氧化能力和肠道消化酶活性的影响, 实验将初始重一致的大鳞副泥鳅随机分为4组, 每组3个重复, 饲养于12个水箱中, 每箱20尾。采用周期性饥饿2d再投喂4d(S2F4)、周期性饥饿2d再投喂6d(S2F6)、周期性饥饿2d再投喂8d(S2F8)和持续投喂(对照组)4种投喂模式, 投喂30d, 并于第0、第15和第30天收集样本进行检测。结果表明: (1)不同处理对末体长和特定生长率无显著影响(P>0.05), S2F8处理组末体重和增重率显著高于对照组(P<0.05)。(2)周期性饥饿再投喂对肥满度、脏体比和肝体比无显著影响(P>0.05)。(3)随饥饿再投喂处理时间增长, S2F6和S2F8组肝脏SOD、CAT和GSH-PX活性显著升高; 在第15天, S2F8组SOD活性显著高于对照组(P<0.05), S2F6和S2F8组肝脏CAT活性显著高于对照组(P<0.05), S2F6和S2F8组肝脏GSH-PX活性均显著高于对照组(P<0.05)。在第30天, S2F6和S2F8组SOD活性显著高于对照组(P<0.05), S2F6组CAT活性均显著高于对照组(P<0.05), S2F6和S2F8组中GSH-PX活性显著高于对照组(P<0.05)。(4)对肠道消化酶研究发现, 投喂时间对肠道蛋白酶、淀粉酶和脂肪酶活性无显著影响。在第30天时, S2F6和S2F8组肠道脂肪酶显著低于对照组(P<0.05)。综上所述, 周期性饥饿再投喂可激发大鳞副泥鳅补偿生长, 引起肝脏抗氧化酶活性增加, 肠道消化酶活性降低。其中S2F8组补偿生长最显著, 且肠道消化酶活性变化程度较小。因此, 为保证饲养效果, 推荐使用S2F8投喂模式。     

Mechanisms of 17beta-estradiol on the production of ET-1 in ovariectomized rats

In order to clarify the mechanism underlying the possible preventive effect of estrogen on atherogenesis, we investigated the role of 17beta-estradiol (E2) in the regulation of endothelin-1 (ET-1) production in ovariectomized rats, which may contribute to atherogenesis. Female Spragure-Dawly rats were randomly divided into three groups: sham-operated group (sham), ovariectomized group (OVX) and 17beta-estradiol replacement group (OVX + E2, 20 microg(-1).kg.d(-1),s.c.). 4 weeks after operation, the plasma concentration of ET-1, clearance of ET-1, functional ECE activity and preproET-1 mRNA expression in aorta were measured. Concentration of plasma ET-1 change from 107.8 +/- 18.3 pg/ml (sham) and 135.5 +/- 27.6 pg/ml (OVX + E2) to 190.7 +/- 25.5 pg/ml (OVX ) (n = 8, p < 0.05). There was no significant difference in the clearance of 125IET-1 among three groups (p > 0.05). Functional ECE activity was increased in OVX group in comparison to that in sham group (p < 0.05). The OVX increased the preproET-1 mRNA expression in sham, whereas treatment with estrogen reversed these changes (p < 0.05). The present study have shown that estrogen down-regulates plasma ET-1 levels by inhibiting the preproET-1 mRNA expression and functional ECE activity. Clearance of ET-1 was not affected. Inhibition of ET-1 production mediated by modulating ECE activity may be one of the novel mechanisms of the protective of estrogens on the cardiovascular system.     

Diazepam effects of peritoneal macrophage activity and corticosterone serum levels in Balb/C mice

In the present experiment we investigate the effects of diazepam on macrophage activity and serum corticosterone levels in mice. Adult mice were treated with diazepam (1.5 mg/kg/day - group E) or with control solution (group C1) for 7 days; some animals were only handled, receiving no treatment (group C2). Oral onco-BCG was used for peritoneal macrophage activation. Diazepam treatment: 1-decreased macrophage spreading and phagocytosis; 2-decreased the concentrations of H2O2 spontaneously but not phorbol myristate-acetate-induced release. In relation to mice of group C1, diazepam treatment increased the serum levels of corticosterone. No differences were detected between data of groups C1 and C2 both for macrophage activity and serum corticosterone levels. The present data were explained on the basis of a synergistically action for diazepam through peripheral type binding sites (PBR) present in both adrenals and macrophages, stimulating adrenal glucocorticoid production and altering the macrophage cytokine network.     

Free Radicals in Rabbit Spinal Cord Ischemia: Electron Spin Resonance Spectroscopy and Correlation with SOD Activity

1. In nonanesthetized rabbits temporal occlusion of the abdominal aorta was used to induce oxidative stress in the lower part of the body including distal segments of the spinal cord.2. Spinal cord samples were taken from the animals exposed to 25-min aortic occlusion (AO ) or to occlusion followed by 1- or 2-hr reperfusion (AO/R1 or AO/R2, respectively) or from sham-operated animals (C). The presence of free radicals (FR) in the spinal cord samples frozen in liquid N₂ was assessed by ESR spectroscopy without spin trapping. Moreover, superoxide dismutase (SOD) activity and conjugated diene (CD) levels were measured in the samples.3. In the AO group FR were detected in the spinal cord regions close to the occlusion (lower thoracic and distal segments) along with a decrease in SOD activity. The calculated g value (g = 2.0291) indicated that the paramagnetic signal recorded might be attributed to superoxide radicals. FR were absent in the AO/R1 group. Concurrently, the SOD activity revealed a significant tendency to return to the control level. FR appeared again in the AO/R2 group, mostly in the upper and middle lumbar regions, along with a decrease in SOD activity. No sample from the C group revealed FR. A significant increase in CD levels was observed in the thoracolumbar region only in the AO/R2 group. The temporary absence of FR in the AO/R1 group suggests activation of defense antioxidant mechanisms (e.g., specific enzymatic systems such as SOD), which might have been exhausted later.4. Changes in SOD activity similar to those observed in the thoracolumbar region, though less noticeable, occurred in the obviously noncompromised tissue (upper cervical region). This points to a kind of generalized reponse of the animal to aortic occlusion.5. Direct ESR spectroscopy revealed the presence of FR as well as their time course in the spinal cord during the early phase of ischemia/reperfusion injury and the inverse relationship between FR and SOD activity.     

Biologically active oligodeoxyribonucleotides-IX. Synthesis and anti-HIV-1 activity of hexadeoxyribonucleotides, TGGGAG, bearing 3′- and 5′-end-modification

We have determined that hexadeoxyribonucleotides (5′TGGGAG3′), with modified aromatic groups such as a trityl group at the 5′-end, have anti-HIV-1 activity in vitro. The 6-mer bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5′-end had the most potent activity and the least cytotoxicity. When the 3′-end of the 5′-(3,4-DBB)-modified 6-mer was substituted with a 2-hydroxyethylphosphate, a 2-hydroxyethylthiophosphate, or a methylphosphate group at the 3′-end, anti-HIV-1 activity increased. Moreover, among various 3′- and 5′-end-modified 6-mers that were tested, the 6-mer (R-95288) bearing a 3,4-DBB group at the 5′-end and a 2-hydroxyethylphosphate group at the 3′-end was the most stable, when incubated with mouse, rat, or human plasma. Therefore, R-95288 was chosen as the best candidate for possible use in therapy on the basis of its anti-HIV-1 activity.     

氧化应激对磷酸三钙磨损颗粒诱导的假体周围骨溶解的影响及其机制

目的：探讨氧化应激对磷酸三钙（TCP）磨损颗粒诱导的假体周围骨溶解的影响及其作用机制。方法：36只雄性ICR小鼠随机分为3组（n=12）：假手术（Sham）组、TCP磨损颗粒（TCP）组和N-乙酰-L-半胱氨酸（NAC）组。将TCP磨损颗粒30 mg包埋于小鼠颅骨顶部构建假体周围骨溶解模型,于术后第2天颅顶骨膜局部注射NAC（1.0 mg/kg）,隔日1次,持续2周后处死动物采血、取颅骨。抗酒石酸酸性磷酸酶（TRAP）染色观察小鼠颅骨假体周围骨溶解情况;ELISA和化学比色法检测血清中肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）、白介素-6（IL-6）和总抗氧化能力（T-AOC）含量及超氧化物歧化酶（SOD）活性;Western blot检测假体周围骨组织中内质网应激标志蛋白葡萄糖调节蛋白78（GRP78）、蛋白激酶R样内质网激酶（PERK）、磷酸化PERK（p-PERK）、真核细胞翻译起始因子2α（eIF2α）和磷酸化eIF2α（p-eIF2α）的表达。结果：与Sham组比较,TCP组小鼠血清TNF-α、IL-1β和IL-6水平及假体周围骨溶解面积显著增加（P<0.05）,T-AOC含量和SOD活性明显降低（P<0.05）,GRP78蛋白质表达、p-PERK/PERK和p-eIF2α/eIF2α值显著升高。与TCP组比较,NAC组小鼠血清TNF-α、IL-1β和IL-6水平及骨溶解面积明显减少（P<0.05）,血清T-AOC含量和SOD活性明显增加（P<0.05）,GRP78蛋白质表达、p-PERK/PERK和p-eIF2α/eIF2α值明显降低。结论：抑制氧化应激可阻止TCP磨损颗粒诱导的假体周围骨溶解,其机制可能与PERK/eIF2α通路的失活有关。     

Enzymological analysis of the tumor suppressor A-C1 reveals a novel group of phospholipid-metabolizing enzymes

A-C1 protein is the product of a tumor suppressor gene negatively regulating the oncogene Ras and belongs to the HRASLS (HRAS-like suppressor) subfamily. We recently found that four members of this subfamily expressed in human tissues function as phospholipid-metabolizing enzymes. Here we examined a possible enzyme activity of A-C1. The homogenates of COS-7 cells overexpressing recombinant A-C1s from human, mouse, and rat showed a phospholipase A_1/2 (PLA_1/2) activity toward phosphatidylcholine (PC). This finding was confirmed with the purified A-C1. The activity was Ca²⁺ independent, and dithiothreitol and Nonidet P-40 were indispensable for full activity. Phosphatidylethanolamine (PE) was also a substrate and the phospholipase A₁ (PLA₁) activity was dominant over the PLA₂ activity. Furthermore, the protein exhibited acyltransferase activities transferring an acyl group of PCs to the amino group of PEs and the hydroxyl group of lyso PCs. As for tissue distribution in human, mouse, and rat, A-C1 mRNA was abundantly expressed in testis, skeletal muscle, brain, and heart. These results demonstrate that A-C1 is a novel phospholipid-metabolizing enzyme. Moreover, the fact that all five members of the HRASLS subfamily, including A-C1, show similar catalytic properties strongly suggests that these proteins constitute a new class of enzymes showing PLA_1/2 and acyltransferase activities.     

人参皂甙Rb1减轻冈田酸诱导的大鼠海马神经元Tau蛋白过度磷酸化

为研究人参皂甙Rb1(ginsenoside Rb1)对冈田酸(okadaic acid,OA)诱导的大鼠海马神经元Tau蛋白过度磷酸化的影响及其可能机制,实验随机分为正常组、溶媒对照组、OA模型组和Rb1预处理组。正常组不作任何处理;Rb1预处理组大鼠分别用5、10、20 mg/kg的Rb1预处理,每天一次,共14 d,于第13天向海马背侧注射1.5μl OA[0.483 μl,溶于10% 二甲基亚砜(dimethysulphoxide,DMSO)];OA模型组大鼠于第13天时海马背侧注射OA,溶媒对照组则注射等体积的生理盐水。各组均于第15天收取标本。通过Biescbowski’s染色、免疫组化和Western blot,分别观察大鼠海马神经元胞体和突起内神经原纤维的改变和磷酸化Tau蛋白的表达水平,同时检测蛋白磷酸酯酶2A(protein phosphatase-2A,PP2A)活性以探讨其作用机制。结果显示:(1)OA模型组与溶媒对照组及正常组比较,海马神经元胞体和突起着色较深,染色不均匀;神经元中Thr231和Sei396位点磷酸化的Tau蛋白和总Tau含量增多;PP2A活性则明显下降(P<0.01):(2)Rb1预处理组大鼠海马神经元胞体和突起染色均匀,神经原纤维走行规则;海马神经元中Thr231和Ser396位点磷酸化的Tau蛋白和总Tau 含量较OA模型组减少,而PP2A活性明显增高(P<0.01)。以上观察结果表明,人参皂甙Rb1可以减轻OA诱导的大鼠海马神经元Tau蛋白过度磷酸化,其机制可能与提高PP2A活性有关。     

血清Visfatin、PRDX1水平与克罗恩病患者活动度指标和肠道菌群的相关性分析

摘要 目的：分析血清内脂素（Visfatin）、过氧化物还原蛋白1（PRDX1）水平与克罗恩病（CD）患者活动度指标和肠道菌群的相关性。方法：选取2019年4月~2022年12月期间联勤保障部队第九一〇医院收治的146例CD患者，根据简化克罗恩病疾病活动指数（CDAI）将所有CD患者分为中重度活动组（n=36）、轻度活动组（n=49）、缓解期组（n=61）。对比三组血清Visfatin、PRDX1、C反应蛋白（CRP）水平、血沉（ESR）、肠道菌群数量。采用Pearson相关性分析血清Visfatin、PRDX1与 CDAI、 CRP、ESR和肠道菌群数量的相关性。结果：中重度活动组、轻度活动组的血清Visfatin、PRDX1水平高于缓解期组，且中重度活动组血清Visfatin、PRDX1水平高于轻度活动组（P<0.05）。中重度活动组、轻度活动组的CRP、ESR高于缓解期组，且中重度活动组CRP、ESR高于轻度活动组（P<0.05）。中重度活动组、轻度活动组的肠球菌、大肠杆菌高于缓解期组，且中重度活动组的肠球菌、大肠杆菌高于轻度活动组（P<0.05），中重度活动组、轻度活动组的双歧杆菌、类杆菌低于缓解期组，且中重度活动组的双歧杆菌、类杆菌低于轻度活动组（P<0.05）。Pearson相关性分析显示，血清Visfatin、PRDX1、 CRP水平与 肠球菌、大肠杆菌菌群数量、CDAI、ESR呈正相关，而与双歧杆菌、类杆菌菌群数量呈负相关（P<0.05）。结论：CD患者的血清Visfatin、PRDX1升高，可导致疾病进展，肠道菌群紊乱加重。