Ramipril treatment suppresses islet fibrosis in Otsuka Long-Evans Tokushima fatty rats

We evaluated whether ramipril, one of long-acting ACEIs, has a direct effect on pancreas islets in animal model of type 2 diabetes. OLETF rats were treated with ramipril for 24 weeks. We assessed the body weight, glucose tolerance, and the amount of islet fibrosis. RT-PCR and Western blot analysis of transforming growth factor-beta with its downstream signals were performed from the pancreas. Ramipril treatment remarkably reduced weight gain and the area under the curve of glucose. Islet fibrosis and the expression of TGF-beta with its downstream signal molecules were significantly reduced in the pancreas of ramipril-treated group than in control and paired-feeding group. These beneficial effects of ramipril might be related to the downregulation of TGF-beta and its downstream signals in OLETF rats. To our knowledge, this is the first report suggesting the potential effect of ramipril on the prevention of islet destruction by fibrosis in the animal model of type 2 diabetes mellitus.     

Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats

Exercise training is commonly prescribed for treatment of nonalcoholic fatty liver disease (NAFLD). We sought to determine whether exercise training prevents the development of NAFLD in Otsuka Long-Evans Tokushima Fatty (OLETF) rats and to elucidate the molecular mechanisms underlying the effects of exercise on hepatic steatosis. Four-week-old OLETF rats were randomly assigned to either a sedentary control group (Sed) or a group given access to voluntary running wheels for 16 wk (Ex). Wheels were locked 2 days before euthanasia in the Ex animals, and both groups were euthanized at 20 wk old. Voluntary wheel running attenuated weight gain and reduced serum glucose, insulin, free fatty acids, and triglycerides in Ex animals compared with Sed (P < 0.001). Ex animals exhibited significantly reduced hepatic triglyceride levels and displayed fewer lipid droplets (Oil Red O staining) and reduced lipid droplet size compared with Sed. Wheel running increased by threefold the percent of palmitate oxidized completely to CO(2) in the Ex animals but did not alter AMP-activated protein kinase-alpha (AMPKalpha) or AMPK phosphorylation status. However, fatty acid synthase and acetyl-coenzyme A carboxylase (ACC) content were significantly reduced (approximately 70 and approximately 35%, respectively), and ACC phosphorylation and cytochrome c content were significantly elevated (approximately 35 and approximately 30%, respectively) in the Ex animals. These results unequivocally demonstrate that daily physical activity attenuates hepatic steatosis and NAFLD in an obese rodent model and suggest that this effect is likely mediated, in part, through enhancement of hepatic fatty acid oxidation and reductions in key protein intermediates of fatty acid synthesis.     

Downregulation of the skeletal muscle pyruvate dehydrogenase complex in the Otsuka Long-Evans Tokushima Fatty rat both before and after the onset of diabetes mellitus

The pyruvate dehydrogenase complex (PDC) catalyzes the irreversible oxidative decarboxylation of pyruvate in mitochondria. The PDC activity is regulated by a phosphorylation/dephosphorylation cycle catalyzed by specific kinases (PDK) and phosphatases (PDP). In this study, the regulatory mechanisms of PDC were examined in skeletal muscle of the spontaneously diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rat before and after the onset of diabetes. The Long-Evans Tokushima Otsuka (LETO) rat was used as control. Plasma glucose and insulin concentrations were at normal levels in both groups at 8 weeks of age but were significantly higher in OLETF than in LETO rats at 25 weeks of age (1.2-fold for glucose and 15-fold for insulin), indicating development of diabetes in the former. Plasma free fatty acids were 1.6-fold concentrated and the skeletal muscle PDC activity state was significantly lower in OLETF than in LETO rats at both ages, suggesting suppression of pyruvate oxidation in OLETF rats even before the onset of diabetes. The PDK activity and the abundance of the PDK isoform 4 protein as well as mRNA were greater in OLETF rats at both ages. Conversely, the abundance of the PDP isoform 1 protein and mRNA was less in OLETF than in LETO rats at both ages. These results suggest that concomitant greater PDK4 and less PDP1 expression in skeletal muscle of OLETF rats before the onset of diabetes are responsible for the lowering of the PDC activity and may be related with the development of diabetes mellitus.     

The effect of dietary polyunsaturated fatty acid on insulin sensitivity and lipid metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats

The effects of insulin sensitivity and lipid metabolism of dietary lard, eicosapentaenoic acid-rich oil (EPA oil) or arachidonic acid oil (AA oil) in Otsuka Long-Evans Tokushima Fatty (OLETF) rats were examined. Blood glucose was not different in each group at 30, 60, 120 min on an oral glucose tolerance test. Fasting blood glucose levels were lower in lard and AA oil groups than in controls. Hepatic triglyceride concentration and liver histochemistry revealed that the fat content was higher in the lard group and the AA oil group than in controls. The EPA oil group showed TG levels as high as the control group. Serum total cholesterol in the EPA oil group was lower, while the level in the AA oil group was higher than in the lard and control groups. HDL cholesterol was 1.5-fold higher in the AA oil group than in controls. Dietary EPA oil or AA oil supplementation showed different effects on lipid metabolism in this model.     

The 10trans,12cis isomer of conjugated linoleic acid suppresses the development of hypertension in Otsuka Long-Evans Tokushima fatty rats

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid found in beef, lamb, and dairy products. CLA has attracted considerable attention over the past several decades because of its potentially beneficial biological effects, including protective effects against several cancers, atherosclerosis, and obesity. Here we provide the first evidence that the 10trans,12cis-CLA isomer is able to suppress increases in blood pressure during the onset of obesity in OLETF rats. After 3 weeks of feeding with 10t,12c-CLA, systolic blood pressure was significantly lowered compared with rats fed linoleic acid or 9c,11t-CLA. Abdominal adipose tissue weight was also significantly lowered in rats fed 10t,12c-CLA, but not in those which were fed 9c,11t-CLA. In addition, we found that the relative mRNA expressions of angiotensinogen and leptin were suppressed by 10t,12c-CLA in adipose tissue. We speculate that the antihypertensive effect of 10t,12c-CLA can be attributed to the lowered secretion of hypertensive adipocytokines from abdominal adipose tissues.     

莪术醇对非酒精性脂肪性肝大鼠肝功能和肝纤维化的影响及机制*

目的:探讨莪术醇(CC)对非酒精性脂肪性肝(NAFLD)大鼠模型肝功能和肝纤维化的影响及机制。方法:采用高脂饮食构建非酒精脂肪肝炎(NASH)伴肝纤维化的大鼠模型,将60只SD大鼠随机分为:空白对照组、模型组(NASH)、NASH+复方鳖甲软肝片(CBT)组(阳性对照组)、NASH+CC组(25、50、100 mg/kg),每组10只。测量大鼠肝脏占体重的百分比,测量大鼠高密度脂蛋白(HDL)、甘油三酯(TG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,HE染色观察肝纤维化情况,免疫组化检测鼠肝组织α-平滑肌肌动蛋白(α-SMA)表达及肝组织核因子κB p65(NF-κB p65)的阳性染色情况,蛋白印迹(Western blot)检测α-SMA、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶抑制剂-1(TIMP-1)蛋白表达及Toll样受体-4(TLR4)、转化生长因子激活激酶-1(TAK1)、NF-κB p65、血管细胞粘附分子-1(VCAM-1)蛋白的表达情况,酶联免疫吸附法(ELISA)检测肝组织中白介素(IL-6、IL-10、IL-1β)、肿瘤坏死因子-α(TNF-α)的表达。结果:与空白对照组相比,模型组大鼠HDL、 IL-10含量、MMP-1蛋白表达量显著降低(P＜0.05),TG、ALT、AST、肝组织P65阳性率,α-SMA、TIMP-1、TLR4、TAK1、NF-κB p65、VCAM-1表达、IL-6、TNF-α及IL-1β含量显著升高(P＜0.05)。与模型组相比,CBT和CC处理后大鼠HDL、 IL-10含量、MMP-1蛋白表达量显著升高(P＜0.05),TG、ALT、AST、肝组织P65阳性率,α-SMA、TIMP-1、TLR4、TAK1、NF-κB p65、VCAM-1表达、IL-6、TNF-α及IL-1β含量显著降低(P＜0.05),其中模型+CC组以高浓度组改善最显著(P＜0.05),但各剂量改善幅度均低于模型+CBT组(P＜0.05)。结论:莪术醇通过调节TLR4、TAK1、NF-κB p65信号通路,减轻炎症反应,改善肝功能,从而缓解非酒精性脂肪肝肝肝纤维化,且在一定范围内呈浓度依赖性。     

Calorie restriction improves whole-body glucose disposal and insulin resistance in association with the increased adipocyte-specific GLUT4 expression in Otsuka Long-Evans Tokushima fatty rats

Calorie restriction (CR) has been shown to improve peripheral insulin resistance and type 2 diabetes in animal models. However, the exact mechanism of CR on GLUT4 expression and translocation in insulin-sensitive tissues has not been well elucidated. In the present study, we examine the effect of CR on the expression of glucose transporter 4 (GLUT4), GLUT4 translocation, and glucose transport activity in adipose tissue from Otsuka Long-Evans Tokushima Fatty (OLETF) rat and control (LETO) rats. CR (70% of satiated group) ameliorated hyperglycemia and improved impaired glucose tolerance (IGT) in OLETF rats. In skeletal muscle, the expression levels of GLUT4 and GLUT1 were not significantly different between LETO and OLETF rats, and were not affected by CR. By contrast, the expression level of GLUT4 was markedly decreased in the adipose tissue of OLETF rats, but was dramatically increased by CR. The GLUT4 recruitment stimulated by insulin was also improved in OLETF rat adipocytes by CR. The insulin-stimulated 2-deoxyglucose (2DG) uptake was significantly increased in adipocytes from the CR OLETF rats, as compared with the satiated OLETF rats. Taken together, these results suggest that CR improves whole body glucose disposal and insulin resistance in OLETF rats, and that these effects may associate with the increased adipocyte-specific GLUT4 expression.     

Aminoguanidine normalizes ET-1-induced aortic contraction in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats by suppressing Jab1-mediated increase in ET(A)-receptor expression

Circulating levels of endothelin (ET)-1 are increased in the diabetic state, as is endogenous ET(A)-receptor-mediated vasoconstriction. However, the responsible mechanisms remain unknown. We hypothesized that ET-1-induced vasoconstriction is augmented in type 2 diabetes with hyperglycemia through an increment in advanced glycation end-products (AGEs). So, we investigated whether treatment with aminoguanidine (AG), an inhibitor of AGEs, would normalize the ET-1-induced contraction induced by ET-1 in strips of thoracic aortas isolated from OLETF rats at the chronic stage of diabetes. In such aortas (vs. those from age-matched genetic control LETO rats): (1) the ET-1-induced contraction was enhanced, (2) the levels of HIF1α/ECE1/plasma ET-1 and plasma CML-AGEs were increased, (3) the ET-1-stimulated ERK phosphorylation mediated by ET(A)-R was increased, (4) the expression level of Jab1-modified ET(A)-R protein was reduced, and (5) the expression level of O-GlcNAcylated ET(A)-R protein was increased. Aortas isolated from such OLETF rats that had been treated with AG (50mg/kg/day for 10 weeks) exhibited reduced ET-1-induced contraction, suppressed ET-1-stimulated ERK phosphorylation accompanied by down-regulation of ET(A)-R, and increased modification of ET(A)-R by Jab1. Such AG-treated rats exhibited normalized plasma ET-1 and CML-AGE levels, and their aortas exhibited decreased HIF1α/ECE1 expression. However, such AG treatment did not alter the elevated levels of plasma glucose or insulin, or systolic blood pressure seen in OLETF rats. These data from the OLETF model suggest that within the timescale studied here, AG normalizes ET-1-induced aortic contraction by suppressing ET(A)-R/ERK activities and/or by normalizing the imbalance between Jab1 and O-GlcNAc in type 2 diabetes.     

肝型脂肪酸结合蛋白研究进展

肝型脂肪酸结合蛋白（liver fatty acid binding protein,L-FABP）是脂肪酸结合蛋白（fatty acid binding proteins,FABPs）家族重要的成员,在肝脏、小肠、肾脏等组织中均有表达。L-FABP在不饱和脂肪酸、饱和脂肪酸、胆固醇、胆汁酸等转运过程中扮演重要角色。目前研究显示L-FABP在脂肪肝、肝硬化以及肝癌发生发展中起到重要作用,并有望作为肝损伤的早期检测指标。此外,新近研究发现尿中L-FABP水平还可以用于预测1型糖尿病患者的临床结局。在2型糖尿病中,尿中L-FABP与糖尿病性肾病的病程有密切关系。主要就L-FABP的特性、结构及其与疾病的关系做一综述。     

Hypoxia inducible factor-1 promotes liver fibrosis in nonalcoholic fatty liver disease by activating PTEN/p65 signaling pathway

Obesity is a major contributor to the development of steatohepatitis and fibrosis from nonalcoholic fatty liver disease (NAFLD). Hypoxia aggravates progression of NAFLD. In mice on high-fat diet (HFD), hepatic steatosis leads to liver tissue hypoxia, evidenced by accumulation of hypoxia inducible factor-1-alpha (HIF-1α), which is a central regulator of the global response to hypoxia. Hepatocyte cell signaling is an important factor in hepatic fibrogenesis. We here hypothesize that HIF-1α knockout in hepatocyte may protect against liver fibrosis. We first found that HFD led to 80% more hepatic collagen deposition than Hif1a^−/−hep mice, which was confirmed by a-SMA staining of liver tissue. Body weight and liver weight were similar between groups. We then found the increasing HIF1a expression and decreasing PTEN expression in the mice on HFD and in PA-treated HepG2 cells. Finally, we found that HIF1 mediated PTEN/nfkb-p65 pathway plays an important role in the development of NAFLD to liver fibrosis. Collectively, these results identify a novel HIF1a/PTEN/NF-κ Bp65 signaling pathway in NAFLD, which could be targeted for the therapy.     

Rare sugar d-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats

A rare sugar, d-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of d-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% d-psicose or 5% d-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, d-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that d-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed d-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. d-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that d-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.     

Long-term fatty liver-induced insulin resistance in orotic acid-induced nonalcoholic fatty liver rats

We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased. However, the liver glycogen content was elevated, and gluconeogenesis genes expressions were obviously decreased at 90 days. The occurrence of fatty liver preceded insulin resistance in OA-induced NAFLD without the interference of obesity and hyperlipidemia, and hepatic insulin resistance may not play a conclusive role in insulin resistance in this model.     

Changes in liver gangliosides in streptozotocin-induced diabetic rats

Diabetes mellitus is associated with various structural and functional liver abnormalities that affect the glycogen and lipid metabolisms. The effects of streptozotocin-induced diabetes and of insulin supplementation to Sprague-Dawley diabetic rats on ganglioside patterns in liver were determined. Diabetic livers showed a tendency to hepatomegaly 3 weeks after STZ-induction of diabetes. The concentration of total gangliosides in diabetic and non-diabetic livers was similar, but the concentration of total gangliosides in the liver of insulin-stabilized rats was slightly increased. Bidimensional TLC chromatographic analysis of gangliosides isolated from normal diabetic and insulin-stabilized diabetic livers showed quantitative and qualitative changes. In comparison with normal controls, the densitometric analyses of diabetic liver ganglioside patterns had increased amounts of GM3, GM1, GD1b, and GT1b gangliosides, while GM2 could not be detected. The hepatic ganglioside pattern of insulin-stabilized diabetic rats was partially restored, resembling the profile of normal rats. The activity of GalNAcT, GalT-2 and SialT-4 transferases was measured in liver microsomal fractions of the different groups of animals. Diabetic rats showed an increased activity of GalNAcT and a decrease in the activity of GalT-2 and SialT-4 compared with the controls. The enzymatic activities found in insulin-treated rats showed a tendency to return to the values observed in normal control animals. The results evidenced that streptozotocin-induced diabetes affects the liver ganglioside pattern and the ganglioside synthesis enzyme activity. The alterations found in ganglioside metabolism could represent one of the earliest changes associated with the diabetic pathology.     

The hedgehog pathway in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of obesity-associated liver diseases and it has become the major cause of cirrhosis in the Western world. The high prevalence of NAFLD-associated advanced liver disease reflects both the high prevalence of obesity-related fatty liver (hepatic steatosis) and the lack of specific treatments to prevent hepatic steatosis from progressing to more serious forms of liver damage, including nonalcoholic steatohepatitis (NASH), cirrhosis, and primary liver cancer. The pathogenesis of NAFLD is complex, and not fully understood. However, compelling evidence demonstrates that dysregulation of the hedgehog (Hh) pathway is involved in both the pathogenesis of hepatic steatosis and the progression from hepatic steatosis to more serious forms of liver damage. Inhibiting hedgehog signaling enhances hepatic steatosis, a condition which seldom results in liver-related morbidity or mortality. In contrast, excessive Hh pathway activation promotes development of NASH, cirrhosis, and primary liver cancer, the major causes of liver-related deaths. Thus, suppressing excessive Hh pathway activity is a potential approach to prevent progressive liver damage in NAFLD. Various pharmacologic agents that inhibit Hh signaling are available and approved for cancer therapeutics; more are being developed to optimize the benefits and minimize the risks of inhibiting this pathway. In this review we will describe the Hh pathway, summarize the evidence for its role in NAFLD evolution, and discuss the potential role for Hh pathway inhibitors as therapies to prevent NASH, cirrhosis and liver cancer.     

Oxidative stress in the pathogenesis of nonalcoholic fatty liver disease,in rats fed with a choline-deficient diet

Background/Aim : The pathogenesis of Nonalcoholic Fatty Liver Disease remains largely unknown, but oxidative stress seems to be involved. The aim of this study was to evaluate the role of oxidative stress in experimental hepatic steatosis induced by a choline-deficient diet. Methods : Fatty liver disease was induced in Wistar rats by a choline-deficient diet. The animals were randomized into three groups: I (G1) and II (G2), n=6 each - fed with a choline-deficient diet for four and twelve weeks respectively; Group III (control-G3; n=6) - fed with a standard diet for twelve weeks. Samples of plasma and liver were submitted to biochemical, histological and oxidative stress analysis. Variables measured included serum levels of aminotransferases (AST, ALT), cholesterol and triglycerides. Oxidative stress was measured by lucigenin-enhanced luminescence and the concentration of hydroperoxides (CE-OOH-cholesteryl ester) in the liver tissue. Results: We observed moderate macro- and microvesicular fatty change in periportal zones G1 and G2 as compared to controls (G3). In G2, fatty change was more severe. The inflammatory infiltrate was scanty and no fibrosis was seen in any group. There was a significant increase of AST and triglycerides in G1 and G2 as compared to control group G3. The lucigenin-amplified luminescence (cpm/mg/min × 10³) was significantly increased in G1 (1393±790) and G2 (7191±500) as compared to controls (513±170), p <0.05. The concentrations of CE-OOH were higher in G1 (5.7±0.9 nmol/mg protein) as compared to control (2.6±0.7 nmol/mg protein), p <0.05. Conclusion: 1) Oxidative stress was found to be increased in experimental liver steatosis; 2) The production of reactive oxygen species was accentuated when liver steatosis was more severe; 3) The alterations produced by oxidative stress could be an important step in the pathogenesis of nonalcoholic fatty liver disease.     

LncRNA MAYA promotes iron overload and hepatocyte senescence through inhibition of YAP in non-alcoholic fatty liver disease

Although recent evidence has shown that hepatocyte senescence plays a crucial role in the pathogenesis and development of non-alcoholic fatty liver disease (NAFLD), the mechanism is still not clear. The purpose of this study was to investigate the signal transduction pathways involved in the senescence of hepatocyte, in order to provide a potential strategy for blocking the process of NAFLD. The results confirmed that hepatocyte senescence occurred in HFD-fed Golden hamsters and PA-treated LO2 cells as manifested by increased levels of senescence marker SA-β-gal, p16 and p21, heterochromatin marker H3K9me3, DNA damage marker γ-H2AX and decreased activity of telomerase. Further studies demonstrated that iron overload could promote the senescence of hepatocyte, whereas the overexpression of Yes-associated protein (YAP) could blunt iron overload and alleviate the senescence of hepatocyte. Of importance, depression of lncRNA MAYA (MAYA) reduced iron overload and cellular senescence via promotion of YAP in PA-treated hepatocytes. These effects were further supported by in vivo experiments. In conclusion, these data suggested that inhibition of MAYA could up-regulate YAP, which might repress hepatocyte senescence through modulating iron overload. In addition, these findings provided a promising option for heading off the development of NAFLD by abrogating hepatocyte senescence.     

Serum adipocyte-specific fatty acid-binding protein is associated with nonalcoholic fatty liver disease in apparently healthy subjects

Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein that is expressed in adipocytes and is closely associated with insulin resistance, metabolic syndrome, and Type 2 diabetes. We investigated the relationship between A-FABP as a surrogate marker of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in apparently healthy subjects. We assessed clinical and biochemical metabolic parameters and measured serum levels of A-FABP, high-sensitivity C-reactive protein and tumor necrosis factor-α (TNF-α) in 494 subjects who were divided into two groups according to the presence of NAFLD by abdominal ultrasonography. All parameters associated with metabolic syndrome were significantly higher in patients with NAFLD (P<.001). A-FABP showed positive correlation with TNF-α, homeostasis model assessment index of insulin resistance (HOMA-IR), and metabolic syndrome (P<.001) when adjusted for age and sex. The odds ratio for the risk of NAFLD in the highest tertile of A-FABP compared with the lowest tertile was 7.36 (CI 3.80-14.27, P<.001) after adjustment for age and sex; 4.52 (CI 2.22-9.20, P<.001) after adjustment for age, sex, HOMA-IR and metabolic syndrome and 2.86 (CI 1.11-7.35, P<.05) after further adjustment for all metabolic parameters including TNF-α. The serum level of A-FABP was independently associated with NAFLD and showed significant correlation with TNF-α, HOMA-IR, and metabolic syndrome.     

双歧杆菌三联活菌肠溶胶囊对高脂饮食所致大鼠非酒精性脂肪肝的疗效及机制探讨

目的 观察微生态制剂贝飞达(双歧杆菌三联活菌肠溶胶囊)治疗高脂饮食所致大鼠非酒精性脂肪肝的疗效并探讨其可能的作用机制.方法 雄性SD大鼠32只,适应性饲养1周后,随机分为3组,正常组:12只给予普通饲料喂养;模型组:12只,贝飞达治疗组:8只,均给予高脂饲料喂养;于喂养12周末正常组及模型组各处死4只,经肝组织HE染色确定造模成功后,贝飞达治疗组给予贝飞达[0.113 g/(kg·d)]灌胃,于16周末全部处死.检测大鼠血清AST、ALT、TC、TG、LDL、HDL、血清内毒素水平,观察其肝组织学变化.结果 模型组于高脂饲料喂养12周末出现脂肪肝,与正常组比较,模型组大鼠血清AST、ALT、TG、TC、LDL、HDL及血清内毒素水平均明显升高(P＜0.01).贝飞达治疗组大鼠各项指标较模型组均有显著改善,肝脏脂肪变性程度减轻.结论 微生态制剂贝飞达可能通过改善肠道菌群紊乱,减轻内毒素血症,从而调节肝脏脂质代谢紊乱,对非酒精性单纯性脂肪肝起到治疗作用.     

An increase of collagen biosynthesis in livers of rats submitted to chronic intoxication with ethanol

Summary It was found that chronic intoxication of rats with ethanol results in a dictinct, progressive increase of 5³H-proline incorporation into collagen synthesized by liver. At the same time biosynthesis of other proline-containing proteins in rat liver slightly decreases. These effects precede the morphological symptoms of liver damage induced by ethanol.