性别对小鼠高脂血症动物模型的影响

目的观察性别对建立小鼠高脂血症动物模型的影响。方法健康成年昆明种小鼠40只,雌雄各半,随机分4组：雄性对照组、雌性对照组、雄性高脂组、雌性高脂组,按各组要求分别给予正常饲料和高脂饲料喂养。连续2周,取血测定实验小鼠血中总胆固醇（total cholesterol,TC）、甘油三酯（triglyceride,TG）、低密度脂蛋白（low density lipoprotein,LDL）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol,HDL-C）含量。结果雌性对照组血脂四项指标与雄性对照组差异不显著,高脂饮食使小鼠血中TC、LDL水平明显增高（P〈0.05）,雌雄组之间差异不显著。结论性别对实验小鼠高脂血症模型的建立及效果无明显影响。     

Heritable, diet-induced hyperlipidemia in California mice (Peromyscus californicus) is due to increased hepatic secretion of very low density lipoprotein triacylglycerol

California mice (Peromyscus californicus) develop type II diabetes mellitus when fed a high-fat diet. We undertook the current studies to determine whether hyperlipidemia precedes the development of insulin resistance and to establish breeding colonies of hyperlipidemic and normolipidemic mice. For 6 wk, mice (n = 24) received a diet containing 25.8% of energy from fat. Mice representing the upper and lower quartiles of serum triacylglycerol (TAG) response (mean, >1000 mg/dl versus <300 mg/dl, respectively; 6 mice per group) were designated as high (HR) and low (LR) responders, respectively, and were used for further study. After 12 wk of consuming the high-fat diet, HR mice remained hypertriglyceridemic and developed hyperinsulinemia (5.1 +/- 1.3 ng/ml), hypercholesterolemia (309.3 +/- 31.0 mg/dl), and hyperglycemia (205.9 +/- 30.3 mg/dl) compared with LR mice. HR mice were not hyperphagic or obese. Offspring of HR x HR mice had elevated serum TAG concentrations (mean, 1752.2 +/- 209.7 mg/dl), hypercholesterolemia, hyperinsulinemia, and mild hyperglycemia by 5.5 mo of age. Mating HR male and LR female mice produced HR, intermediate, and LR progeny. HR mice had elevated serum concentrations of cholesterol, and plasma concentrations of high density lipoprotein cholesterol, and the very low density lipoprotein TAG compared with LR mice. Lipoprotein lipase and hepatic lipase activities did not differ between HR and LR mice. Studies of in vivo hepatic TAG production indicated that the hyperlipidemia of HR mice is a consequence of TAG hypersecretion.     

Endogenous Androgen Deficiency Enhances Diet-Induced Hypercholesterolemia and Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice

BackgroundDespite numerous clinical and animal studies, the role of sex steroid hormones on lipoprotein metabolism and atherosclerosis remain controversial.ObjectiveWe sought to determine the effects of endogenous estrogen and testosterone on lipoprotein levels and atherosclerosis using mice fed a low-fat diet with no added cholesterol.MethodsMale and female low-density lipoprotein receptor-deficient mice were fed an open stock low-fat diet (10% of kcals from fat) for 2, 4, or 17 weeks. Ovariectomy, orchidectomy, or sham surgeries were performed to evaluate the effects of the presence or absence of endogenous hormones on lipid levels, lipoprotein distribution, and atherosclerosis development.ResultsFemale mice fed the study diet for 17 weeks had a marked increase in levels of total cholesterol, triglycerides, apolipoprotein-B containing lipoproteins, and atherosclerosis compared with male mice. Surprisingly, ovariectomy in female mice had no effect on any of these parameters. In contrast, castration of male mice markedly increased total cholesterol concentrations, triglycerides, apolipoprotein B-containing lipoproteins, and atherosclerotic lesion formation compared with male and female mice.ConclusionsThese data suggest that endogenous androgens protect against diet-induced increases in cholesterol concentrations, formation of proatherogenic lipoproteins, and atherosclerotic lesions formation. Conversely orchidectomy, which decreases androgen concentrations, promotes increases in cholesterol concentrations, proatherogenic lipoprotein formation, and atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice in response to a low-fat diet.     

参麦注射液对高脂血症大鼠血脂的调节作用

目的：通过观察参麦注射液对高脂血症模型大鼠的血脂水平和一系列相关生化指标的影响,探讨其对高脂血症模型大鼠血脂的调节作用。方法：30只SPF级雄性SD大鼠用基础饲料适应性喂养1周,随机分为3组（n=10）：对照组,模型对照组,参麦注射液组。对照组用基础饲料喂养,模型对照组和参麦注射液组用高脂饲料喂养,每周测定动物体重一次。参麦注射液组每天给予2次参麦注射液10 ml/kg,连续灌胃45 d。之后测定大鼠血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、超氧化物歧化酶（SOD）、谷胱甘肽过氧物酶（GSH-Px）、丙二醛（MDA）、脂蛋白酯酶（LPL）和肝酯酶（HL）活性。结果：模型对照组大鼠体重、血清中TC、TG、LDL-C和MDA水平较对照组明显升高（P<0.01）,而HDL-C、SOD、GSH-Px、LPL和HL水平明显降低（P<0.01）。参麦注射液组大鼠体重、血清中TC、TG、LDL-C和MDA水平较模型对照组明显降低（P<0.01）,而HDL-C、SOD、GSH-Px、LPL和HL水平明显升高（P<0.05,P<0.01）。结论：参麦注射液对高脂模型大鼠的血脂具有较明显的调节作用,并具有抗脂质过氧化的作用。     

降脂益生菌对非酒精性脂肪性肝病小鼠胆汁酸代谢及转运的影响和机制初探

目的 探讨降脂益生菌(鼠李糖乳杆菌DM9054和植物乳杆菌86066联合制剂)对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)小鼠胆汁酸代谢及转运的影响和可能机制。 方法 18只雄性FXR / 小鼠随机分为3组(n=6):正常饮食组、高脂饮食组和高脂饮食+降脂益生菌组。其中正常饮食组给予普通饮食和生理盐水灌胃,高脂饮食组给予高脂饮食和生理盐水灌胃,高脂饮食+降脂益生菌组给予高脂饮食和降脂益生菌灌胃。所有小鼠干预12周,处死小鼠1周前行胰岛素耐量试验和腹腔注射葡萄糖耐量试验。小鼠处死后自动生化分析仪检测血脂、胆汁酸及肝功能指标;RT PCR检测肝脏和回肠组织炎症因子相对表达量;HE染色评估肝脏和回肠组织病理情况;Western blot检测法尼醇受体(Farnesoid X receptor,FXR)通路中的成纤维细胞生长因子15(fibroblast growth factor 15,FGF15)、成纤维细胞生长因子受体4(fibroblast growth factor receptor 4,FGFR4)和小分子异源二聚体(short heterodimer partner,SHP)、胆汁酸合成限速酶胆固醇7α 羟化酶(cholesterol 7α hydroxylase,CYP7A1)及胆汁酸转运相关的胆盐输出泵(bile salt export pump,BSEP)的蛋白表达。 结果 和高脂饮食组相比,高脂饮食+降脂益生菌组小鼠血清中胆汁酸含量明显下降(P=0.000 1),FGF15、FGFR4和BSEP蛋白表达水平升高(P=0.009 7、0.024 2、0.000 1),CYP7A1的蛋白表达水平降低(P=0.006 9)。此外,通过降脂益生菌干预还明显改善了高脂饮食FXR / 小鼠的糖脂代谢紊乱(P=0.002 4)、肝脏脂肪变性、肝脏和回肠组织炎症(P=0.013 8、0.000 1、0.000 1)以及肠黏膜屏障功能(P=0.014 2)。 结论 降脂益生菌具有类似选择性肠道FXR激动剂的作用,能够通过调控肠道FXR FGF15通路改善胆汁酸的代谢及转运,进而缓解高脂饮食FXR / 小鼠的NAFLD。     

Effects of phenotype, sex, and diet on plasma lipids in LA/N-cp rats

The LA/N-corpulent (cp) rat is a recently developed congenic strain which exhibits obesity. The effects of phenotype and sex on serum and lipoprotein lipid content were examined in LA/N-cp rats fed either a control or an atherogenic diet high in saturated fat and protein. Obese rats were pair-fed to equivalent lean animals. Results from this study indicate that sex, phenotype, and diet exert significant effects on plasma and lipoprotein cholesterol content. Plasma cholesterol levels were higher in obese compared with lean rats, females than in males, and rats consuming the atherogenic diet compared with the control diet. Plasma and lipoprotein triglyceride levels were significantly increased only in obese compared with lean animals. The increased plasma cholesterol and triglyceride was observed primarily in the chylomicron and very low density lipoprotein fractions. Increased levels of plasma cholesterol were not a result of increased dietary cholesterol absorption or increased liver cholesterol biosynthesis. These data suggest that LA/N-cp rats can serve as a unique rodent model for the study of the interrelationships between hyperlipidemia, obesity, and coronary heart disease.     

Effect of Diets Containing Sucrose vs. D‐tagatose in Hypercholesterolemic Mice

Effects of functional sweeteners on the development of the metabolic syndrome and atherosclerosis are unknown. The objective was to compare the effect of dietary carbohydrate in the form of sucrose (SUCR) to D‐tagatose (TAG; an isomer of fructose currently used as a low‐calorie sweetener) on body weight, blood cholesterol concentrations, hyperglycemia, and atherosclerosis in low‐density lipoprotein receptor deficient (LDLr^−/−) mice. LDLr^−/− male and female mice were fed either standard murine diet or a diet enriched with TAG or SUCR as carbohydrate sources for 16 weeks. TAG and SUCR diets contained equivalent amounts (g/kg) of protein, fat, and carbohydrate. We measured food intake, body weight, adipocyte diameter, serum cholesterol and lipoprotein concentrations, and aortic atherosclerosis. Macrophage immunostaining and collagen content were examined in aortic root lesions. CONTROL and TAG‐fed mice exhibited similar energy intake, body weights and blood glucose and insulin concentrations, but SUCR‐fed mice exhibited increased energy intake and became obese and hyperglycemic. Adipocyte diameter increased in female SUCR‐fed mice compared to TAG and CONTROL. Male and female SUCR‐fed mice had increased serum cholesterol and triglyceride concentrations compared to TAG and CONTROL. Atherosclerosis was increased in SUCR‐fed mice of both genders compared to TAG and CONTROL. Lesions from SUCR‐fed mice exhibited pronounced macrophage immunostaining and reductions in collagen content compared to TAG and CONTROL mice. These results demonstrate that in comparison to sucrose, equivalent substitution of TAG as dietary carbohydrate does not result in the same extent of obesity, hyperglycemia, hyperlipidemia, and atherosclerosis.     

Synthetic low and high fat diets for the study of atherosclerosis in the mouse

Diets currently used to produce atherosclerotic lesions in mice are often undefined and cause accumulation of fat in the liver and gallstone formation. Therefore, synthetic low and high fat diets of known composition were formulated in this study. A synthetic diet containing 50% sucrose, 15% cocoa butter, 1% cholesterol, and 0.5% sodium cholate was found to produce a depression in high density lipoprotein cholesterol (HDL-C) and an elevation of very low density lipoprotein (VLDL) and low density lipoprotein cholesterol (LDL-C) in the atherosclerosis-susceptible strain, C57BL/6J. This diet was able to consistently produce aortic lesions and led to a decrease in liver damage and gallstone formation. The synthetic low fat diet did not produce HDL-C levels as high as those found in mice fed chow, but resulted in similar VLDL/LDL-C levels. Lipoprotein and apolipoprotein parameters were compared in C57BL/6J and the atherosclerosis-resistant strain, C3H/HeJ, consuming the synthetic low fat or high fat diets. As reported earlier, when consuming a high fat diet C57BL/6J mice have significantly lower HDL-C and apoA-I levels than C3H/HeJ mice. Further analysis shows that the molar ratio of plasma HDL-C to apoA-I is significantly lower in C57BL/6J mice, suggesting that HDL in the susceptible strain has a lower cholesterol-carrying capacity. This conclusion is consistent with the observation that the HDL particle size is smaller for C57BL/6J mice than for C3H/HeJ. Both strains increased their apoE levels when fed the synthetic high fat diet, but C3H/HeJ mice had higher levels of apoE on both diets. The major response to consumption of the high fat diet for both strains was an increase in apoB-48 from 5 micrograms/ml on a low fat diet to 54 and 109 micrograms/ml for C57BL/6J and C3H/HeJ, respectively. ApoB-100 showed minimal response to the high fat diet. The defined high fat diet can be used to study atherosclerosis in the mouse since it produces aortic lesions but reduces or eliminates other pathological changes such as gallstone formation and liver damage.     

A Murine Model of Obesity With Accelerated Atherosclerosis

The epidemic of obesity sweeping developed nations is accompanied by an increase in atherosclerotic cardiovascular diseases. Dyslipidemia, diabetes, hypertension, and obesity are risk factors for cardiovascular disease. However, delineating the mechanism of obesity‐accelerated atherosclerosis has been hampered by a paucity of animal models. Similar to humans, apolipoprotein E–deficient (apoE^?/?) mice spontaneously develop atherosclerosis over their lifetime. To determine whether apoE^?/? mice would develop obesity with accelerated atherosclerosis, we fed mice diets containing 10 (low fat (LF)) or 60 (high fat (HF)) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total cholesterol, triglycerides, or leptin concentrations. Plasma concentrations of the acute‐phase reactant serum amyloid A (SAA) are elevated in both obesity and cardiovascular disease. Accordingly, plasma SAA concentrations were increased fourfold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro‐ and antiatherogenic lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the antiatherogenic lipoprotein high‐density lipoprotein (HDL). Moreover, SAA was localized with apoB‐containing lipoproteins and biglycan in the vascular wall. Taken together, these data suggest male apoE‐deficient mice are a model of metabolic syndrome and that chronic low level inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.     

A gender-specific role for phosphatidylethanolamine N-methyltransferase-derived phosphatidylcholine in the regulation of plasma high density and very low density lipoproteins in mice

Phosphatidylethanolamine N-methyltransferase (PEMT)is involved in a secondary pathway for production of phosphatidylcholine (PC) in liver. We fed Pemt-/-mice a high fat/high cholesterol diet for 3 weeks to determine whether or not PC derived from PEMT is required for very low density lipoprotein secretion. Lipid analyses of plasma and liver indicated that male Pemt-/- mice accumulated triacylglycerols in their livers and were unable to secrete the same amount of triacylglycerols from the liver as did Pemt+/+ mice. Plasma levels of triacylglycerol and both apolipoproteins B100 and B48 were significantly decreased only in male Pemt-/- mice. Experiments in which mice were injected with Triton WR1339 showed that, whereas hepatic apoB100 secretion was decreased in male Pemt-/- mice, the decrease in plasma apoB48 in male Pemt-/- mice was not due to reduced secretion. Moreover, female and, to a lesser extent, male Pemt-/- mice showed a striking 40% decrease in plasma PC and cholesterol in high density lipoproteins. These results suggest that, even though the content of hepatic PC was normal in PEMT-deficient mice, plasma lipoprotein levels were profoundly altered in a gender-specific manner.     

藤三七类黄酮组分对小鼠代谢综合征模型及其肠道菌群的调节作用

目的 探究类黄酮组分对小鼠代谢综合征模型及肠道菌群的调节作用。方法 SPF级雄性BALB/c小鼠分为对照组（NFD）、模型组（HFD）、类黄酮组（HFD+fla）,每组6只。采用高脂饲料和高果糖建立代谢综合征模型,处理8周。类黄酮组用100 mg/(kg•d)藤三七类黄酮灌胃。记录动物进食量和饮水量,测空腹血糖和体重。第8周处死动物,解剖获取肝脏和附睾脂肪组织。测定总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）含量。小鼠肝脏组织切片进行HE染色观察。取小鼠粪便,应用PCR-DGGE技术分析肠道菌群。结果 模型组小鼠TC明显高于对照组（P=0.000）,类黄酮组TC显著低于模型组（P=0.007）。模型组LDL-C显著高于对照组（P=0.031）,类黄酮组LDL与模型组差异无统计学意义（P=0.072）,但有降低趋势。肝脏脏器系数与脂肪系数组间比较差异无统计学意义（F=1.891,P=0.185）,但类黄酮组与模型组相比,有降低趋势;模型组小鼠血清TG较对照组降低,组间比较差异有统计学意义（F=7.738,P=0.005）。模型组小鼠HDL较对照组升高,组间比较差异无统计学意义（F=3.621,P=0.052）;肝脏病理学结果显示,类黄酮组肝细胞水肿得到了明显改善。模型组小鼠肠道菌群多样性和拟杆菌属细菌低于对照组;类黄酮组相比于模型组,肠道菌群多样性和拟杆菌属细菌有所恢复,嗜胆菌属细菌增加。结论 藤三七类黄酮组分能促进肠道主要益生菌的生长,可以显著降低BALB/c小鼠TC水平,并有降低血清LDL-C的趋势。类黄酮明显改善小鼠肝细胞水肿,促进肠道菌群的恢复。     

富硒益生菌的功效研究进展

硒是人体必需的微量元素,对人体健康有重要作用。益生菌能够将硒元素转化为有机硒,降低硒的毒性,同时硒又提高了益生菌的生物活性,富硒益生菌具备了硒和益生菌的双重功效。本文主要综述了近年来富硒益生菌的功效,如抗氧化、抑制有害菌、调节肠道菌群、抗癌等。     

三种金花茶提取物降脂作用实验研究

目的:探讨金花茶浓缩液、金花茶乙酸乙酯/二氯甲烷提取物以及金花茶水提物对高脂血症小鼠血脂的调节作用。方法:将小鼠按照体重随机分成正常饮食组和高脂饮食组,分别给予正常饲料和高脂饲料喂食,4周后将高脂饮食小鼠按照体重以及血脂水平(TC)随机分成金花茶浓缩液组、金花茶乙酸乙酯/二氯甲烷提取物组、金花茶水提物组以及辛伐他丁组。3种金花茶提取物以及辛伐他丁混悬液连续灌胃10周,同时给予高脂饮食。末次给药后禁食不禁水12 h,摘眼球取血,检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)以及丙二醛(MDA)。结果:与模型组相比,金花茶浓缩液和辛伐他丁能显著降低血清TC、TG、LDL-C水平(P0.01或P0.05),但是对HDL-C无明显调节作用;对血清中的AST、ALT、SOD以及MDA影响不大。金花茶乙酸乙酯/二氯甲烷提取物以及水体物对血清中的TC、TG、LDL-C、HDL-C、AST、ALT、SOD及MDA无明显的调节作用。结论:金花茶浓缩液对高脂血症小鼠的血脂具有良好的调节作用。     

Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice

Resistin has been linked to components of the metabolic syndrome, including obesity, insulin resistance, and hyperlipidemia. We hypothesized that resistin deficiency would reverse hyperlipidemia in genetic obesity. C57Bl/6J mice lacking resistin [resistin knockout (RKO)] had similar body weight and fat as wild-type mice when fed standard rodent chow or a high-fat diet. Nonetheless, hepatic steatosis, serum cholesterol, and very low-density lipoprotein (VLDL) secretion were decreased in diet-induced obese RKO mice. Resistin deficiency exacerbated obesity in ob/ob mice, but hepatic steatosis was drastically attenuated. Moreover, the levels of triglycerides, cholesterol, insulin, and glucose were reduced in ob/ob-RKO mice. The antisteatotic effect of resistin deficiency was related to reductions in the expression of genes involved in hepatic lipogenesis and VLDL export. Together, these results demonstrate a crucial role of resistin in promoting hepatic steatosis and hyperlipidemia in obese mice.     

Hyperlipidemia is a major determinant of neointimal formation in LDL receptor-deficient mice

LDL receptor-deficient (LDLR(-/-)) mice exhibit mild hyperlipidemia on a chow diet but develop severe hyperlipidemia on a high fat diet. In this study, we investigated neointimal formation after removal of the endothelium when LDLR(-/-) mice were fed chow or a Western diet containing 42% fat, 0.15% cholesterol, and 19.5% casein. At 10 weeks of age, female mice underwent endothelial denudation of the left common carotid artery. Two weeks after injury, neointimal formation was barely detectable in the injured vessel when mice developed mild hyperlipidemia on the chow diet. In contrast, neointimal lesions were obvious when mice developed severe hyperlipidemia on the Western diet. Immunohistochemical and histological analyses demonstrated the presence of macrophage foam cells and smooth muscle cells in neointimal lesions. The injured artery also exhibited a significant increase in medial area on the Western diet. Plasma levels of MCP-1 and soluble VCAM-1 were significantly elevated by feeding of the Western diet. These data indicate that hyperlipidemia aggravates neointimal growth in LDLR(-/-) mice by promoting foam cell formation and inflammation.     

益生菌干预对肥胖孕鼠子代菌群及脂代谢的影响

目的分析高脂高糖饮食诱导肥胖母亲对子代菌群及脂代谢影响。方法C57BL/6J雌性小鼠30只随机分为正常对照组、肥胖组、益生菌干预组,每组10只。分别给予标准饲料、高脂高糖饲料以及高脂高糖饲料同时给予益生菌,连续喂养6周,制成肥胖母鼠模型。6周后雌、雄鼠合笼,受孕,孕期继续上述饮食。产后母乳喂养,3周后处死。留取雌性子鼠第21天粪便样本进行PCR-DGGE分析,同时酶反应比色法分析子鼠血脂情况。结果与正常对照组子代相比,肥胖母鼠子代菌群结构出现异常,益生菌干预组子代肠道菌群失调状况明显改善;肥胖母鼠子代血清总胆固醇、低密度脂蛋白含量升高,益生菌干预组子代血脂异常情况明显改善。结论高脂高糖饮食诱导肥胖母亲子代存在肠道菌群紊乱及脂代谢异常,益生菌干预母亲有利于改善子代菌群紊乱及脂代谢异常。     

Atherogenic diet alters folate enzymes in mice: implications of folate deficient homocysteinemia.

The two key enzymes, methylenetetrahydrofolate reductase and methionine synthase involved in methionine synthesis from homocysteine were studied in atherogenic diet fed mice. Methylenetetrahydrofolate reductase activity was elevated while methionine synthase was impaired in atherogenic diet fed group. Impaired methionine synthase activity would adversely affect the methionine synthesis from homocysteine, resulting in a rise in the homocysteine levels, which are atherogenic. This is reflected by the increased levels of very low density and low density lipoprotein cholesterol values and a higher ratio for total cholesterol to high density lipoprotein cholesterol.     

降脂益生菌调节胆固醇代谢 改善小鼠非酒精性脂肪肝

目的研究一种由鼠李糖乳杆菌DM9054和植物乳杆菌86066构成的降脂益生菌组合对非酒精性脂肪性肝病(NAFLD)小鼠胆固醇代谢的影响及其可能机制。方法 24只雄性LDLR-/-小鼠随机分为对照组、模型组和益生菌干预组。高脂饮食(HFD)15周建立小鼠NAFLD模型,造模同时干预组给予鼠李糖乳杆菌DM9054联合植物乳杆菌86066灌胃,对照组和模型组给予等量生理盐水灌胃。实验过程中监测各组小鼠体重变化。实验结束后,检测小鼠血清甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)和高密度脂蛋白胆固醇(HDL)的水平差异。检测小鼠肝脏组织病理变化。使用Realtime PCR检测小鼠肠道内法尼脂受体(FXR)mRNA、顶端膜钠依赖的胆汁酸转运体(ASBT)mRNA、纤维生长因子15(FGF-15)mRNA和三磷酸腺苷结合盒转运体G5(ABCG-5)mRNA表达水平。Western blot检测小鼠肝脏胆固醇7α-羟化酶(CYP7A1)、FXR、三磷酸腺苷结合盒转运体G8(ABCG-8)、清道夫受体BI(SR-BI)、3-羟基-3-甲基戊二酸单酰辅酶A还原酶(HMGCR)、胆盐输出泵(ABCB-11)、纤维生长因子受体4(FGFR-4)和胆固醇调节元件结合蛋白-2(SREBP-2)蛋白表达水平。结果与模型组相比,降脂益生菌干预组小鼠体重减轻(P0.05);小鼠血清TC、TG、LDL水平降低,HDL水平升高(P0.05);小鼠肝脏脂肪变性和炎性细胞浸润的现象显著减少;小鼠肠道ASBT mRNA和ABCG-5mRNA表达水平明显降低(Ps0.05),FGF-15mRNA表达水平明显升高(P0.05),FXR mRNA表达水平差异无统计学意义(P0.05);小鼠肝脏FGFR-4蛋白表达水平升高(P0.05),SREBP-2和HMGCR蛋白表达水平降低(Ps0.05),FXR、CYP7A1、SR-BI、ABCG-8和ABCB-11蛋白表达水平差异无统计学意义(Ps0.05)。结论降脂益生菌可能通过激活FXR-FGF15通路调节胆汁酸代谢;通过下调SREBP-2表达水平,抑制HMGCR表达,减少胆固醇的生成,从而起到改善非酒精性脂肪肝的作用。     

Hypercholesterolemia promotes a CD36-dependent and endothelial nitric-oxide synthase-mediated vascular dysfunction

Numerous studies have implicated either the presence or absence of CD36 in the development of hypertension. In addition, hypercholesterolemia is associated with the loss of nitric oxide-induced vasodilation and the subsequent increase in blood pressure. In the current study, we tested the hypothesis that diet-induced hypercholesterolemia promotes the disruption of agonist-stimulated nitric oxide generation and vasodilation in a CD36-dependent manner. To test this, C57BL/6, apoE null, CD36 null, and apoE/CD36 null mice were maintained on chow or high fat diets. In contrast to apoE null mice fed a chow diet, apoE null mice fed a high fat diet did not respond to acetylcholine with a decrease in blood pressure. Caveolae isolated from in vivo vessels did not contain endothelial nitric-oxide synthase and were depleted of cholesterol. Age-matched apoE/CD36 null mice fed a chow or high fat diet responded to acetylcholine with a decrease in blood pressure. The mechanism underlying the vascular dysfunction was reversible because vessels isolated from apoE null high fat-fed mice regained responsiveness to acetylcholine when incubated with plasma obtained from chow-fed mice. Further analysis demonstrated that the plasma low density lipoprotein fraction was responsible for depleting caveolae of cholesterol, removing endothelial nitric-oxide synthase from caveolae, and preventing nitric oxide production. In addition, the pharmacological removal of caveola cholesterol with cyclodextrin mimicked the effects caused by the low density lipoprotein fraction. We conclude that the ablation of CD36 prevented the negative impact of hypercholesterolemia on agonist-stimulated nitric oxide-mediated vasodilation in apoE null mice. These studies provide a direct link between CD36 and the early events that underlie hypercholesterolemia-mediated hypertension and mechanistic linkages between CD36 function, nitric-oxide synthase activation, caveolae integrity, and blood pressure regulation.     

大黄醇提液抗家兔实验性高脂血症及脂肪肝的实验研究

目的:检验大黄醇提液抗家兔实验性高脂血症及脂肪肝的影响。方法:将30只雄性健康白兔随机分为5组(n=6):对照组给予基础饲料;模型组给予高脂饲料;三个大黄组给予高脂饲料同时分别灌胃不同药量的大黄醇提液。实验过程中进行一般性指标观测,检测不同阶段五组家兔血脂水平,检测脂肪肝病变程度。结果:大黄醇提液具有降低血清甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C),升高高密度脂蛋白胆固醇(HDL-C),降低肝细胞脂肪变性的作用。并且大黄醇提液的以上作用存在一定的量效关系。结论:大黄醇提液可降低动脉粥样硬化兔模型的血脂水平、降低脂肪肝的发生发展。