Dietary fiber and cholesterol metabolism in rats fed a high cholesterol diet.

The effect of administering blackgram (Phaseolus mungo) fiber (isolated as neutral detergent residue) at the 30% dietary level has been studied with regard to lipid concentration in the tissues and that of biliary and fecal bile acids and sterols. Rats were fed a high fat-cholesterol diet and compared with those fed a cellulose diet. The results indicate that blackgram fiber significantly lowers cholesterol in both serum and aorta [11]. There was an increased concentration of biliary sterols and bile acids and increased fecal excretion of sterols and bile acids, each of these effects being significantly greater than those observed in the rats fed cellulose.     

艾塞那肽对糖尿病大鼠肝脏组织胰岛素抵抗的影响

目的 研究胰高糖素样肽1受体激动剂艾塞那肽对高脂喂养联合小剂量链脲佐菌素诱导的糖尿病大鼠肝脏组织胰岛素抵抗的影响及其机制.方法 健康雄性6周龄SD大鼠采用随机数字法分为正常对照组（C组,n=6）、正常对照＋艾塞那肽处理组（C＋E组,n=6）、糖尿病组（D组,n=5）以及糖尿病＋艾塞那肽处理组（D＋E组,n=5）,由高脂饮食加小剂量STZ诱导成2型糖尿病后,D＋E组以及C＋E组大鼠予艾塞那肽,5μg腹部皮下注射,每天1次干预;8周后,分别测定空腹葡萄糖出现率、肝糖输出率、甘油出现率、甘油糖异生相关参数;测定外源性胰岛素持续输注状态下的肝糖输出和葡萄糖输注率.同时行透射电子显微镜观察大鼠肝脏组织超微结构改变.多组间数据比较采用单因素方差分析.结果 D＋E组大鼠空腹血糖、血浆甘油三酯、总胆固醇、低密度脂蛋白、稳态模型胰岛素抵抗指数（HOMA-IR）水平均显著低于D组,但显著高于C组及C＋E组,差异均有统计学意义（F=82.827、81.648、27.613、26.300、105.234,均P＜0.05）,ISI则显著高于D组大鼠,但仍显著低于C组及C＋E组（F=17.566,P＜0.05）.空腹状态下,D＋E组大鼠的葡萄糖出现率、甘油出现率、肝糖输出率、甘油糖异生相关参数（甘油转化为葡萄糖的百分率、来源于甘油的葡萄糖百分比、甘油糖异生速率）均显著低于D组大鼠,但仍显著高于C组及C＋E组（F=68.424、41.543、68.424、40.223、17.491、86.465,均P＜0.05）.胰岛素钳夹稳态时,D＋E组大鼠内源性肝糖输出较D组大鼠显著抑制,但仍显著高于C组及C＋E组（F=85.403,P＜0.05）;其外源性葡萄糖输注率则显著高于D组大鼠,仍显著低于C组及C＋E组（F=49.954,P＜0.05）.超微结构研究显示D＋E组大鼠的肝细胞超微结构损伤显著减轻.结论 胰高糖素样肽1受体激动剂艾塞那肽显著改善糖尿病大鼠肝脏组织超微结构损伤,进而改?     

Effects of high cholesterol high fat diet on plasma lipoproteins in familial hypercholesterolemia

Heterozygous individuals with familial hypercholesterolemia possess about half of the normal numbers of functioning receptors on their cells. This is thought to be responsible for their hypercholesterolemia. In normals, dietary cholesterol increases LDL production and decreases LDL receptor-related LDL clearance, resulting in elevations in LDL cholesterol levels of ～30 mg/dL. To assess the effects of high fat and high cholesterol diets on the lipoproteins of individuals with diminished LDL receptors, three kinds of diets, including ones high in cholesterol, were fed to four patients with familial hypercholesterolemia, in the expectation that diet effects on apoB- or apoE-containing lipoproteins would be exaggerated. The basal diet consisted of 15% protein, 30% fat, 55% carbohydrate, 300 mg/d cholesterol, $\text{P}\text{S}$ ratio 0.4; the high fat diet was identical except that fat calories were 55% and carbohydrate 30%; the high fat-high cholesterol diet was identical with the high fat diet except ～750 or ～1,500 mg/d of cholesterol were added. Each diet was eaten for five weeks at home and for the sixth week at the general Clinical Research Center. Fasting (12–14 hours) plasmas were collected every two weeks for lipoprotein-lipid and apoprotein quantitation. At the end of each period, fasting and 4-hour postprandial samples were analyzed also by zonal ultracentrifugation and gel permeation chromatography. The significant results were as follows: (1) on analysis of fasting samples on the fat + Chol diet, measures of the levels of VLDL (ie, VLDL lipids, VLDL protein on zonal ultracentrifugation, VLDL-associated lipids, and apoE on chromatography) fell; measures of LDL were not consistently changed; and measures of HDL₂ and HDL_c rose. Compositions of VLDL were altered, ie, mass % of triglycerides fell and cholesterol rose. Zonal effluent profiles of VLDL, LDL, HDL₂, and HDL₃ were not altered, nor were gel chromatographic elution patterns of cholesterol, triglycerides, apoB, apoA-I, and apoE, suggesting that the sizes and/or densities of lipoproteins were not altered. Therefore, the numbers of VLDL particles must have fallen and the numbers of HDL₂ and HDL_c must have risen. The nature and magnitude of the changes fell within the range of changes previously observed in normolipidemic subjects. The data indicate that having diminished numbers of LDL receptors did not affect the abilities of these patients to resist diet-induced qualitative or quantitative alterations of their plasma lipoproteins. Clearly other adaptive mechanisms can compensate for the diminished numbers of LDL receptors.     

胰岛素治疗对高脂喂养的糖尿病大鼠胰腺内脂质及葡萄糖刺激后胰岛素分泌的影响

目的 观察胰岛素治疗对高脂喂养的糖尿病（DM）大鼠胰腺内脂质及葡萄糖刺激后胰岛素分泌（GSIS）的影响。方法 Wistar大鼠随机分为正常对照组（NC），DM高脂饲养组（DH）及DM高脂饲养胰岛素治疗组（DHI）。测定血糖、胰岛素、FFA、TG、胰腺内TG和FFA、胰岛素蛋白表达和相对β细胞数量、计算△I30／△G30及β细胞胰岛素分泌指数（MBCI）。结果 与DH相比，DHI血TG和FFA下降虽无统计学意义，但胰腺内TG和FFA含量明显下降（P〈0．01），△I30／△G30、MBCI、胰岛素表达和相对β细胞数量得到明显改善（P〈0．05或P〈0．01）。结论 长期高脂喂养DM大鼠可导致脂质异位沉积于胰腺，并进一步损伤GSIS。GSIS受损可能与胰岛素合成降低，β细胞数量减少有关。胰岛素治疗对高脂所致的上述改变有一定的改善作用。     

Effects of a high protein diet on the evolution of diabetes in streptozotocin-induced and spontaneously diabetic “BB” wistar rats

Summary Recently, we demonstrated a reduction in the diabetogenic action of streptozotocin (STZ) in rats previously adapted to a high protein (HP) diet. These data suggested that amelioration of diabetes resulted from the combination of two effects of the HP diet: initial protection against the diabetogenic action of the drug at the time of exposure and subsequent improvement of the induced diabetic condition. The present study evaluated the effects of a HP diet on the evolution of the metabolic condition in rats with STZ-induced or spontaneous diabetes (BB Wistar rats). Two days after STZ injection, the animals were given isocaloric HP (70% protein, 8% fat) or control (66% carbohydrate, 16% protein, 8% fat) diets for 15 days. After 13 days, the STZ-treated rats fed HP diet showed an impressive decrease in severity of diabetes, as judged by rate of body weight change, plasma glucose, urine volume and glycosuria, serum and pancreatic insulin. The BB Wistar rats, already diabetic for 5 weeks before being transferred to the HP or control diet, were treated with daily injections of insulin. After 31 days on the HP diet, the BB rats showed reduced insulin requirement, reduced blood and urinary glucose levels, but no difference in body weight gain or pancreatic insulin content. The data show that short-term use of HP diets can greatly improve the diabetic condition in STZ-treated animals, but that the beneficial effects of the diet are much less marked in rats with chronic spontaneous diabetes. These data suggest that the ameliorating effect of HP diet is fully manifested only when the diabetic rats have a sufficient number of residual functioning B-cells.     

Heart sarcolemmal ATPase and calcium binding activities in rats fed a high cholesterol diet

ATPase and calcium binding activities were studied in sarcolemmal membranes from hearts of male rats fed either a control or 2% cholesterol diet for different time periods. Studies with isolated membrane revealed a significant increase in Na+-K+ ATPase activity, sialic acid content and ATP-independent calcium binding capacity in the presence of 1.25 mM CaCl2 in the 6 week cholesterol fed group. By 12 weeks, Na+-K+ ATPase, Mg2+-ATPase and Ca2+-ATPase activities as well as ATP-independent calcium binding in the presence of 0.05 mM CaCl2 were increased in membranes from cholesterol fed rats. A significant increase (P less than 0.05) in the sarcolemmal cholesterol/phospholipid molar ratio, which is an indicator of a decrease in membrane fluidity, was also noted in the 12 week cholesterol fed group. Concanavalin A, which is believed to decrease membrane fluidity, stimulated both Mg2+ and Ca2+-dependent ATPase activities and increased ATP-independent calcium binding in control sarcolemmal preparations and these changes resembled those observed in the sarcolemma from cholesterol fed rats. Since concanavalin A did not alter the activity of Na+-K+ ATPase, it appears that some of the observed differences in sarcolemmal activities upon cholesterol feeding did not correlate well with changes in membrane order. At 24 weeks, there was a generalized depression in the sarcolemmal ATPase activities of the cholesterol group; both Mg2+ ATPase and Ca2+ ATPase were significantly less than in control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypercholesterolemic effect of Bacopa monniera linn. on high cholesterol diet induced hypercholesterolemia in rats

ObjectiveTo explore the effect of alcoholic extract of Bacopa monniera (AEBM) on high cholesterol diet-induced rats.MethodsThe shade-dried and coarsely powdered whole plant material (Bacopa monniera) was extracted with 90% ethanol, finally filtered and dried in vacuum pump. The experimental rats were divided into 4 groups: control (group-I), Rats fed with hypercholesterolemic diet (HCD) for 45 days [4% cholesterol (w/w) and 1% cholic acid], Rats fed with HCD for 45 days+AEBM (40mg/kg, body weight/day orally) for last 30 days (group-III) and AEBM alone (group-IV). Blood and tissues (Aorta) were removed to ice cold containers for various biochemical and histological analysis.ResultsAEBM treatment significantly decreased the levels of TC, TG, PL, LDL, VLDL, atherogenic index, LDL/HDL ratio, and TC/HDL ratio but significantly increased the level of HDL when compared to HCD induced rats. Activities on liver antioxidant status (SOD, CAT, GPx, GR, GST) were significantly raised with concomitant reduction in the level of LPO were obtained in AEBM treated rats when compared to HCD rats. Treatment with AEBM significantly lowered the activity of SGOT, LDH and CPK. Histopathology of aorta of cholesterol fed rat showed intimal thickening and foam cell deposition were noted.ConclusionsThese results suggests that AEBM extended protection against various biochemical changes and aortic pathology in hypercholesterolemic rats. Thus the plant may therefore be useful for therapeutic treatment of clinical conditions associated hypercholesterolemia.     

Factors involved in rosuvastatin induction of insulin sensitization in rats fed a high fat diet

Background and AimTo investigate whether rosuvastatin can improve insulin sensitivity in overweight rats having a high fat diet (HFD). The potential mechanisms involved in this action were evaluated, including SIRT-1, other factors involved in glucose metabolism and stress signaling pathways.Methods and ResultsMale Wistar rats (n = 30) were divided into three groups: (i) rats fed a standard diet (3.5% fat); (ii) rats fed a HFD (33.5% fat); and (iii) rats fed a HFD and treated with rosuvastatin (15 mg/kg/day). Evolution: 7 weeks. HFD rats showed increased body, epididymal and lumbar adipose tissue weights. Plasma levels of cholesterol, triglycerides, VLDL, glucose and insulin and leptin/adiponectin ratio were higher in HFD rats, and rosuvastatin treatment reduced them. SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 protein levels in white adipose tissue (WAT) were lower, and JNK was higher in HFD rats compared to controls. Rosuvastatin treatment normalized expression of these mediators. Endothelium-dependent relaxation was reduced in mesenteric rings from HFD rats compared to controls and rosuvastatin enhanced it in HFD rats.ConclusionRosuvastatin treatment reduced insulin resistance without affecting body weight or WAT loss in HFD rats. Reduction of leptin and JNK, and enhancement of SIRT-1, p53, PGC-1α, PPAR-γ and GLUT-4 expression in WAT could contribute to insulin sensitization. Normalization of SIRT-1 expression in WAT could be considered a key novel mechanism that aids in explaining the beneficial effects of rosuvastatin on the amelioration of glucose metabolism and the arrangement of multiple signaling pathways participating in insulin resistance in overweight HFD rats.     

二甲双胍对高脂饲养大鼠肝脏脂肪变的干预作用

目的:探讨胰岛素抵抗在非酒精性脂肪性肝发病中的作用及机制,观察二甲双胍对高脂饲养大鼠肝脏脂肪变的干预效果.方法:21只(?) Wistar大鼠分为3组,每组7只,普通饮食组(SD),高脂饮食组(HF),二甲双胍组(HF- Met)在高脂饮食的同时给予二甲双胍,共8wk.8 wk末处死大鼠,称量附睾脂肪,计算肝指数,生化方法测定ALT、AST、TG、TC、FFA、SOD和MDA.放免法测定空腹胰岛素,逆转录聚合酶链反应(RT-PCR)和ELISA法检测肝脏TNF-αmRNA和蛋白的表达,用葡萄糖输注率(GIR)来评价胰岛素敏感性,并观察肝组织病理变化.结果:与HF相比,HF-Met肝细胞脂肪变和小叶炎症明显减轻,肝指数、胰岛素、AST、ALT、TG、FFA显著下降(3.25±0.26 vs 4.29±0.12,33.37±8.34 vs 46.73±5.24,17.29±5.34 vs 43.48±6.21,4.10±2.47 vs 12.05±4.05,P<0.01;106.0±31.04 vs 141.37±24.87,48.31±16.11 vs 88.34±21.94,P<0.05)TNF-α的表达也显著下降,GIR增加(7.58±1.05 vs 6.31±1.28,P<0.05).结论:二甲双胍干预能明显改善高脂饲养大鼠的胰岛素抵抗,降低肝脏TG、FFA和TNF-α的表达,减轻肝脏脂肪变的程度,提示胰岛素增敏治疗可能是NAFLD防治的一种积极策略.     

胰岛素治疗对高脂喂养的糖尿病大鼠胰岛B细胞分泌变化的影响

目的观察胰岛素治疗对长期高脂喂养的糖尿病(DM)大鼠B细胞分泌功能的影响。方法2003-08~2004-11对华中科技大学同济医学院附属协和医院内分泌实验室的DM大鼠随机分为糖尿病正常饮食组(DN,n=10)、糖尿病高脂饮食组(DH,n=10)、糖尿病高脂饮食胰岛素治疗组(DHI,n=10)及正常Wistar大鼠正常饮食对照组(NC,n=10)。于胰岛素治疗后行口服葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT),并根据血糖和血胰岛素值计算糖负荷后胰岛素增值与血糖增值的比值(ΔI30/ΔG30)和修正的B细胞胰岛素分泌指数(MBCI)。留取空腹血浆测定游离脂肪酸(FFA)和甘油三酯(TG)。留取尾部胰腺组织测定胰腺内TG和FFA。结果与DN组和NC组相比,DH组血和胰腺内TG及FFA计量明显增多(分别为对DN组,P<0·01、P<0·01;对NC组,P<0·01、P<0·01;对DN组,P<0·01、P<0·05;对NC组,P<0·01、P<0·01),此外,ΔI30/ΔG30和MBCI显著降低(分别为对DN组,P<0·01、P<0·05,对NC组,P<0·01、P<0·01)。胰岛素治疗后,与DH组相比,胰腺内TG和FFA计量明显下降(分别为P<0·01、P<0·01),同时ΔI30/ΔG30、MCBI均得到明显改善(P<0·01、P<0·05)结论长期高脂饮食喂养可导致T2DM大鼠胰腺内FFA和TG沉积,并进一步损伤胰岛B细胞胰岛素的分泌;胰岛素治疗对高脂饮食所致的上述影响有一定的改善作用。     

Progression of induced aortic atherosclerosis in rabbits fed a high cholesterol diet

In this study we have evaluated the progression of atheromatosis in aortic arch, thoracic aorta and abdominal aorta in rabbits fed a high cholesterol diet. The aortic atheromatosis decreased progressively from the aortic arch to the abdominal aorta after 6 months of high cholesterol diet. It is possible that a different segmental resistance to hypercholesterolemic damage may be involved in the cranio caudal progression of atheromatosis in rabbits.     

胰岛素治疗对高脂喂养的糖尿病大鼠胰岛B细胞分泌变化的影响

目的 观察胰岛素治疗对长期高脂喂养的糖尿病（DM）大鼠B细胞分泌功能的影响。方法 2003—08—2004-11对华中科技大学同济医学院附属协和医院内分泌实验室的DM大鼠随机分为糖尿病正常饮食组（DN，n=10）、糖尿病高脂饮食组（DH，n=10）、糖尿病高脂饮食胰岛素治疗组（DHI，n=10）及正常Wistar大鼠正常饮食对照组（NC，n=10）。于胰岛素治疗后行口服葡萄糖耐量试验（OGTF）和胰岛素释放试验（IRT），并根据血糖和血胰岛素值计算糖负荷后胰岛素增值与血糖增值的比值（A130／AG30）和修正的B细胞胰岛素分泌指数（MBCU。留取空腹血浆测定游离脂肪酸（FFA）和甘油三酯（TG）。留取尾部胰腺组织测定胰腺内TG和FFA。结果 与DN组和NC组相比，DH组血和胰腺内TG及FFA计量明显增多（分别为对DN组，P〈0．01、P〈0．01；对NC组，P〈0．01、P〈0．01；时DN组，P〈0．01、P〈0．05；对NC组，P〈0．01、P〈0．01），此外，△130／ΔG30和MBCI显著降低（分别为对DN组，P〈0．01、P〈0．05，对NC组，P〈0．01、P〈0．01）。胰岛素治疗后，与DH组相比，胰腺内TG和FFA计量明显下降（分别为P〈0．01、P〈0．01），同时A130／AG30、MCBI均得到明显改善（P〈0．01、P〈0．05）.结论 长期高脂饮食喂养可导致T2DM大鼠胰腺内FFA和TG沉积，并进一步损伤胰岛B细胞胰岛素的分泌；胰岛素治疗对高脂饮食所致的上述影响有一定的改善作用。     

Atherosclerosis in lemmings and voles fed a high fat, high cholesterol diet.

Two species of lemmings and two species of voles were fed a high fat, high cholesterol diet for several months. Clethrionomys rutilus had a moderate (2x) rise in serum cholesterol while Microtus oeconomus had a marked increase (5x); Dicrostonyx stevensoni and Dicrostonyx rubricatus had extreme increases (8x and 11x, respectively). Typical lesions of atherosclerosis were observed in all species, but D. rubricatus had significantly more severe lesions. Hepatic fatty infiltration was the principal pathologic lesion found besides atherosclerosis in those test rodents which died spontaneously.     

Involvement of semicarbazide-sensitive amine oxidase-mediated deamination in atherogenesis in KKAy diabetic mice fed with high cholesterol diet

AIMS/HYPOTHESIS: Semicarbazide-sensitive amine oxidase has been recognised to be a potential risk factor in vascular disorders associated with diabetic complications and to be related to mortality in patients suffering from heart disease. This enzyme, associated with the vascular system, catalyses the deamination of methylamine and aminoacetone, and also acts as an adhesion molecule related to leucocyte trafficking and inflammation. The deaminated products include the toxic aldehydes, formaldehyde and methylglyoxal, respectively, hydrogen peroxide and ammonia. MATERIALS AND METHODS: In this study, the KKAy mouse, a strain possessing features closely resembling those of Type II (non-insulin-dependent) diabetes mellitus has been used to substantiate the hypothesis. Vascular lesions were induced via chronic feeding of a high cholesterol diet. RESULTS: Both MDL-72974A, a selective mechanism-based semicarbazide-sensitive amine oxidase inhibitor and aminoguanidine effectively inhibited aorta semicarbazide-sensitive amine oxidase activity, and caused a substantial increase in urinary methylamine, and a decrease in formaldehyde and methylgloxal levels. Inhibition of semicarbazide-sensitive amine oxidase also reduced oxidative stress, as shown by a reduction of malondialdehyde excretion. Both MDL-72974A and aminoguanidine reduced albuminuria, proteinuria and the number of atherosclerotic lesions in animals fed with a cholesterol diet over a period of treatment for 16 weeks. CONCLUSION/INTERPRETATION: Increased semicarbazide-sensitive amine oxidase-mediated deamination could be involved in the cascade of atherogenesis related to diabetic complications.     

Influence of chronic stress on the compositions of hepatic cholesterol and triglyceride in male Wistar rats fed a high fat diet

Aim: We determined the influence of chronic stress (CS) on the compositions of hepatic cholesterol and triglyceride (TG) in rats fed a high fat diet (HFD). Methods: Male Wistar rats were fed either a standard diet or a HFD and half of the HFD fed rats were given CS (electric foot shock assisted with noise) for 8 weeks. Results: Compared with the control group, the levels of hepatic total cholesterol (TC) and TG were significantly elevated in the HFD and HFD with chronic stress (HFD+CS) groups, and the more severe elevations of them were found in the HFD group. Inversely, the more severe elevations of hepatic water‐soluble parts of TC and TG were found in the HFD+CS group, as the elevations of low‐density lipoprotein cholesterol, very low‐density lipoprotein cholesterol in liver and serum, tumor necrosis factor‐α, interleukin‐1β and malondialdehyde in liver. Meanwhile, downregulated mRNA expressions of hepatic liver X receptor‐α (LXR‐α) and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) were also more severe in the HFD+CS group. Conclusion: CS can aggravate the high levels of water‐soluble compositions of hepatic TC and TG induced by HFD as it aggravates hepatic inflammation and oxidative stress; in spite of that, however, it cannot further promote hepatic lipidosis. This is consistent with the downregulated mRNA expressions of LXR‐α and PPAR‐γ.     

Effects of physical training on the myocardium of streptozotocin-induced diabetic rats

Summary Effects of endurance swimming training on myocardial contractility and left ventricular myosin isoenzymes were examined in diabetic rats. A diabetic condition was induced in 15-weck-old male Wistar rats, by intravenous injection of streptozotocin (50 mg/kg). Swimming training was carried out for five to six weeks (90 min/day, 6 days/week). In order to estimate myocardial contractility, the isometric developed tension of the isolated left ventricular papillary muscle was measured. Myosin isoenzymes were obtained by pyrophosphate gel electrophoresis. Fasting blood glucose of the trained group was significantly lower than that of the sedentary group (sedentary vs. trained=409.6±25.9 vs. 266.3±20.5 mg/dl, p<0.001). There was no significant difference in isometric developed tension (T) between the two groups, and the dT/dt_max of the trained group showed a tendency to increase (sedentary vs. trained, T: 2.8±0.8 vs. 2.9±0.8 g/mm², dT/dt_max: 23.1±3.6 vs. 26.2±3.5 g/mm² · 2, p<0.1). Myocardial mechanical responses to isoproterenol and dibutyryl cAMP were increased in the trained group. Left ventricular myosin isoenzyme pattern was shifted towards VM-1 by endurance swimming (sedentary vs. trained, VM-1: 5.6±4.5 vs. 19.6±8.8%, p<0.001, VM-3: 75.1±10.0 vs. 54.9±14.7%, p<0.001). These results indicate that endurance swimming can improve disordered glucose metabolism and also influence myocardial contractility, myocardial catecholamine responsiveness, and energetics in myocardial contraction.     

Ethanol-induced liver fibrosis in rats fed high fat diet

Severe hepatic steatosis and focal necrosis of hepatocytes have previously been induced in rats by continuous intragastric infusion of ethanol and a diet containing only 5% fat as a per cent of total calories as reported by us previously. Since the ethanol diet fed ad libitum with such a low level of fat has previously failed to produce alcoholic fatty liver, continuously high blood alcohol levels achieved in this model appeared to be key in induction of the progressive pathologic lesions in the liver. In the current study, effects of increased fat intake on alcohol-induced liver injury were investigated. Seventeen pairs of male Wistar rats were implanted with gastrostomy cannulas and infused with a liquid diet containing 25% of total calories as fat plus ethanol or isocaloric dextrose. Ethanol intake was progressively increased from 32% up to 47% of total calories to maintain sustained intoxication for 30 to 120 days. Light and electron microscopic examination of the liver revealed moderate to severe fatty infiltration in all of the ethanol-fed rats, of which 14 had spotty or zonal necrosis in the centrilobular areas accompanied by polymorphonuclear and mononuclear cell infiltration. In addition, fibrosis was observed in association with the necrotic lesions or with large-droplet steatosis. Reticulin and trichrome stains clearly demonstrated fine fibrosis, including perivenular fibrosis as well as septum formation progressing to bridging fibrosis. Furthermore, increased numbers of Ito cells and myofibroblasts were observed in the perivenular fibrotic areas. These results demonstrate striking potentiation of alcohol-induced liver injury by the increased fat intake or by the concomitant decrease in carbohydrate intake.(ABSTRACT TRUNCATED AT 250 WORDS)     

增龄对高脂喂养大鼠胰岛素抵抗和骨骼肌内脂肪的影响

目的探讨增龄对高脂喂养大鼠胰岛素抵抗(IR)和骨骼肌内脂肪影响的可能机制。方法将雄性Wistar4～5月龄大鼠16只和22～24月龄大鼠16只分别随机分为青年对照组和老年对照组,青年高脂组和老年高脂组(高脂饲料喂养),每组8只。8周后,行葡萄糖耐量试验,测定0、30、60和120min的血糖和葡萄糖曲线下面积(AUC);采用正葡萄糖-高胰岛素钳夹试验的葡萄糖输注率(GIR)评价IR。结果与老年对照组和青年对照组比较,老年高脂组和青年高脂组GIR降低,骨骼肌TG及长链酯酰辅酶A(LCACoA)明显升高,差异有统计学意义(P<0.05,P<0.01);与老年对照组比较,老年高脂组大鼠各时间点血糖及AUC比较,差异均有统计学意义(P<0.05,P<0.01)。GIR与胰岛素、骨骼肌TG及LCACoA呈负相关。结论老年和高脂喂养大鼠骨骼肌TG和LCACoA含量增加,可能是老年容易发生IR的原因之一。     

Effects of chronic exercise on endothelial dysfunction and insulin signaling of cutaneous microvascular in streptozotocin-induced diabetic rats.

BACKGROUND: Abnormalities of the modulatory roles played by the endothelium and/or smooth muscle may be critical and initiating factors in the development of diabetic vascular disease. Decreased phosphatidylinositol 3-kinase (PI3-K)/Akt pathway activity and impaired nitric oxide production through this pathway may play pivotal roles in the diabetes-induced vascular dysfunction. Several findings have demonstrated that exercise training has therapeutic and protective effects in type 1 diabetes and could correct endothelial dysfunction. The molecular mechanisms, however, are only partially understood. METHOD: Male Wistar rats (220+/-10 g, N=60) were made diabetic by streptozotocin (60 mg/kg, subcutaneously). After 1 week of diabetes induction, animals were submitted to exercise training for 10 weeks on a treadmill. To characterize cutaneous microvascular responses by laser Doppler flowmetery, animals were deeply anesthetized by intraperitoneal injection of pentobarbital sodium (60 mg/kg) and placed on a heating pad. A rectal thermometer was inserted and body temperature was maintained at 37+/-0.5 degrees C. A tracheotomy was performed to minimize respiratory difficulties. Systemic arterial blood pressure and heart rate were measured by using a tail-cuff during assessment of cutaneous blood flow. RESULTS: (i) Acetylcholine-induced cutaneous perfusion were increased significantly by training in the diabetic groups; (ii) Cutaneous microvascular responses to sodium nitroprusside did not alter in control and diabetic animals by training; and (iii) Local microinjection of insulin increased cutaneous blood flow in trained diabetic and trained control rats compared with age-matched sedentary diabetic and sedentary control normal rats. The administration of wortmannin (PI3K inhibitor) and N-nitro-L-arginine ( nitric oxide synthase inhibitor) before insulin, however, attenuated the increase in cutaneous blood flow in trained diabetic and normal rats. CONCLUSIONS: Chronic exercise improved endothelium-dependent dilatation and potentiated insulin vascular function, possibly by PI3-kinase pathway in diabetic rats.