Roux-en-Y胃旁路术对肥胖大鼠脂肪肝的影响及机制研究

Impact of Roux-en-Y gastric bypass surgery on fatty liver in rats with high-fat diet-induced obesity and its mechanism

关键词:  Roux-en-Y胃旁路术  非酒精性脂肪肝  糖类应答元件结合蛋白  固醇调节原件结合蛋白-1c  大鼠

Key words:  Roux-en-Y gastric bypass surgery  nonalcoholic fatty liver disease  carbohydrate response element binding protein  sterol regulatory element-binding transcription factor 1c  rat

摘要:

目的探讨Roux-en-Y胃旁路术(Roux-en-Y gastric bypass surgery, RYGB)对肥胖大鼠脂肪肝的影响及可能的机制。方法 将30只8周龄雄性Wistar大鼠随机分为正常饮食组(ND组)、高脂饮食组(HFD组)及高脂饮食且接受RYGB组(HFD+RYGB组),每组10只,分别给予正常饮食、高脂饮食。饲养16周后,对HFD+RYGB组大鼠行RYGB,对ND组及HFD组行假手术。术后,ND组大鼠继续给予正常饮食,HFD组与HFD+RYGB组大鼠接受高脂饮食。术后第4周,处死大鼠,收集血样,采用ELISA法测定大鼠血清TG、TC、游离脂肪酸(free fatty acid, FFA)浓度。观察大鼠肝脏外形,取肝脏组织,行H-E染色及油红O染色,显微镜下观察肝脏组织的病理学变化。采用real-time PCR检测肝组织糖类应答元件结合蛋白(ChREBP)、固醇调节原件结合蛋白-1c(SREBP-1c)和乙酰辅酶A羧化酶(ACC)mRNA表达水平。结果 HFD组大鼠体质量、肝脏湿重及内脏脂肪总量高于ND组(P＜0.05),HFD+RYGB组大鼠体质量、肝脏湿重及内脏脂肪总量低于HFD组(P＜0.05)；HFD大鼠血清TG、TC、FFA水平高于ND组(P＜0.05),HFD+RYGB组大鼠血清TG、TC、FFA水平低于HFD组(P＜0.05)；HFD组肝脏TG、TC含量高于ND组(P＜0.05),HFD+RYGB组大鼠肝脏TG、TC低于HDF组(P＜0.05)；H-E及油红O染色结果显示,HFD+RYGB组干细胞脂质沉积、脂滴空泡减少；术后第4周,HFD+RYGB组大鼠肝脏中的ChREBP和SREBP-1c的mRNA的表达量较HFD组均显著降低(P＜0.05)。结论 RYGB能显著缓解肝脏脂肪沉积及血脂,其机制可能与抑制脂肪酸合成途径的关键分子ChREBP和SREBP-1c有关。

Abstract:

Objective To investigate the impact of Roux-en-Y gastric bypass surgery(RYGB) on fatty liver in rats with high-fat diet-induced obesity and its mechanism. Methods Thirty Wistar rats were randomly divided into three groups with 10 in each group. Rats in ND group were fed with normal diet, rats in HFD and HFD +RYGB groups were fed with high-fat diet; after 16 weeks, rats underwent sham operation in ND group and HFD group, and RYGB in HFD plus RYGB group. All rats were sacrificed after 4 weeks of operation. Total body weight, liver weight and visceral fat were measured. Serum triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) concentrations were measured by ELISA. Hepatic tissues were harvested, pathological changes were observed by H-E and oil red O staining. The expressions of carbohydrate response element binding protein (ChREBP), sterol regulatory element-binding transcription factor 1c (SREBP-1c) and acetyl-CoA carboxylase (ACC) mRNA were detected by Real-time PCR. Results Total body weight, liver weight and visceral fat in HFD group were higher than those in ND group(P＜0.05); compared with HFD group, those indicators were decreased in HFD plus RYGB group(P＜0.05). Serum TG, TC, FFA concentrations in HFD group were higher than those in ND group(P＜0.05); compared with HFD group, those indicators were decreased in HFD plus RYGB group(P＜0.05). TG, TC concentrations in liver in HFD group were higher than those in ND group(P＜0.05); compared with HFD group, those indicators were decreased in HFD plus RYGB group(P＜0.05). H-E and oil red O staining showed that hepatic cell lipid, lipid vacuoles decreased in HFD plus RYGB group. Compared with HFD group, the expressions of ChREBP and SREBP-1c mRNA decreased in HFD plus RYGB group after 4 weeks of operation(P＜0.05). Conclusion RYGB can reduce visceral fat and blood lipid, alleviate the deposition of TG and TC in the liver, improve the fatty infiltration and vacuolar degeneration in the liver, down-regulate the expressions of ChREBP and SREBP-1c mRNA in rats with high-fat diet-induced obesity.