Roux-en-Y胃旁路术降低肥胖2型糖尿病大鼠肝脂毒性的探究

Roux-en-Y gastric bypass reduces hepatic lipid toxicity in obese type 2 diabetic rats

目的观察Roux-en-Y胃旁路术(RYGB)后2周肥胖2型糖尿病(T2DM)大鼠肝脂肪代谢及交感神经活性变化,探讨RYGB降低肝脂毒性的可能机制。方法将32只大鼠随机分为正常对照组、肥胖T2DM组、RYGB假手术组和RYGB手术组,每组8只;除正常对照组大鼠外,其余24只采用高脂饮食联合腹腔注射30 mg/kg链脲佐菌素(STZ)诱导肥胖T2DM大鼠模型。采用清醒状态扩展高胰岛素-正血糖钳夹技术评估术后2周大鼠肝胰岛素的敏感性,酶法检测大鼠血浆和肝组织中三酰甘油(TG)及游离脂肪酸(FFA)含量,Western blot检测大鼠肝组织中二酰甘油酰基转移酶2(DGAT2)、磷酸化激素敏感性脂肪酶(p-HSL)、肉碱棕榈酰转移酶(CPT1A)、微粒体三酰甘油转运蛋白(MTTP)和酪氨酸羟化酶(TH)的蛋白表达,ELISA检测血浆NE浓度。结果与肥胖T2DM组和RYGB假手术组相比,术后2周RYGB手术组大鼠体质量降低,血浆TG及FFA减少,血糖恢复正常水平,肝胰岛素敏感性指数提高近1倍(P<0.05),肝组织内TG含量下降超80%(P<0.05),FFA下降近50%(P<0.05),肝组织内DGAT2蛋白表达减少(P<0.05),MTTP蛋白表达差异无统计学意义(P>0.05),p-HSL、CPT1A和TH蛋白表达显著增加(P<0.05)。各组大鼠血浆NE浓度比较差异无统计学意义(P>0.05)。结论RYGB能够减少肝内脂肪蓄积,改善肝胰岛素抵抗。术后肝组织局部交感神经活性上调,肝脂肪分解代谢增强可能是肝脂肪蓄积减少的机制之一。

Objective To investigate the effects of Roux-en-Y gastric bypass on hepatic sympathetic nerve activity and lipometabolism in obese type 2 diabetic rats 2 weeks later,and its possible mechanism is explored.Methods A total of 32 rats were randomly divided into normal control group,obese type 2 diabetic group,RYGB sham group and RYGB group,with 8 rats in each group.In addition to the normal control group,the remaining 24 rats were treated with high-fat diet combined with intraperitoneal injection of 30 mg/kg streptozotocin(STZ)to induce the obese T2DM rat model.The hyperinsulinemic-euglycemic clamp with tracer infusion was completed to assess insulin sensitivity.The levels of triacylglycerol(TG) and free fatty acid(FFA) in plasma and liver were detected by enzymic method.The protein expressions of diacylglycerol acyltransferase2(DGAT2),phospho-hormone-sensitive triglayceride lipase(p-HSL),carnitine palmitoyltransferase 1A (CPT1A),microsomal triglyceride transfer protein (MTTP) and tyrosine 3-monooxygenase (TH) in liver were detected by Western blot.And the concentration of norepinephrine(NE) in plasma was detected by ELISA. Results After 2 weeks,compared with obese type 2 diabetic group and RYGB sham group,the body mass of the rats in RYGB group was decreased,plasma TG and FFA were decreased,blood glucose returned to normal level,and liver insulin sensitivity index was nearly doubled ( P <0.05),and TG content in liver was decreased more than 80%( P <0.05),and hepatic FFA level was decreased nearly 50%( P <0.05),the protein expression of DGAT2 in liver was decreased( P <0.05 ),the expressions of p-HSL,CPT1A and TH in liver were significantly increased 2 weeks after surgery ( P <0.05).There was no significant difference in the protein expression of MTTP in liver and plasma NE between groups. Conclusion RYGB can reduce hepatic lipid toxicity and improve hepatic insulin resistance,the local sympathetic nerve activity of liver tissues is up-regulated after operation,and the enhanced catabolism of liver fat may be one of the mechanisms of decreasing the liver fat accumulation.