Roux-en-Y胃转流术后长期维持减重效应和血糖稳态的机制研究

Mechanism of long-term maintenance of weight loss and blood glucose homeostasis after Roux-en-Y gastric bypass

目的探究Roux-en-Y胃转流术(RYGB)后长期维持减重效应和血糖稳态的机制。方法选用12周龄雄性Sprague Dawley(SD)大鼠作为动物模型,采用完全随机法分为假手术组(n=22)、RYGB组(n=12)和胰腺大部切除术组(n=10),以普通饲料和45%高脂饲料干预8周,检测各组大鼠胰岛素分泌水平、葡萄糖输注率、体重和血糖水平,并通过基因芯片和免疫印迹试验检测各组大鼠脂肪组织代谢通路等的变化。组间比较采用t检验及方差分析。结果与假手术相比,RYGB组大鼠术后空腹及葡萄糖刺激后血浆胰岛素水平均显著降低[(1.3±0.2)比(0.6±0.1)ng/ml,t=3.6,P<0.01;(4.1±0.4)比(2.1±0.3)ng/ml,t=4.3,P<0.01],且在45%高脂饲料喂养的情况下可长期维持空腹胰岛素及体重在较低水平[(3.1±0.3)比(0.7±0.1)ng/ml,t=8.1,P<0.01;(453±11)比(349±6)g,t=8.5,P<0.01]。机制研究发现,大鼠RYGB术后脂肪组织胰岛素信号通路受到抑制(1.0±0.1比0.5±0.1,t=6.4,P<0.01),脂肪酸合成减少,脂肪酸分解增加,腺嘌呤核糖核苷酸依赖的蛋白激酶表达增强(1.0±0.1比1.4±0.1,t=4.0,P<0.01)。与假手术组比较,胰腺大部切除术组空腹血浆胰岛素和胰高血糖素水平分别降低71.7%和68.0%[(1.10±0.10)比(0.30±0.04)ng/ml,t=7.5,P<0.01;(16.2±0.8)比(5.2±0.9)pmol/L,t=9.1,P<0.01],但空腹血糖无明显升高,在普通饲料和45%高脂饲料喂养时体重均显著低于假手术组[(434±13)比(389±5)g,t=3.1,P<0.05;(548±16)比(433±11)g,t=6.0,P<0.01]。结论RYGB术后通过减少能量摄入及避免高胰岛素血症可长期维持低体重和血糖稳态,其机制与脂肪合成代谢抑制,而分解代谢增强密切相关。

Objective To explore the mechanism of long-term maintenance of weight loss and blood glucose homeostasis after Roux-en-Y gastric bypass(RYGB).Methods 12 weeks old male Sprague Dawley(SD)rats were used as animal models and randomly divided into Sham group(n=22),RYGB group(n=12)and pancreatectomy group(n=10),and were with normal diet or high-fat diet for 8 weeks.The levels of insulin secretion,glucose infusion rate,body weight and blood glucose were measured,and the metabolic pathways of adipose tissue were detected by gene chip and western blot.The t test and variance analysis were used to compare the difference among the three groups.Results Compared with Sham group,the fasting and glucose stimulated plasma insulin in SD rats were significantly reduced after metabolic surgery[(1.3±0.2)vs(0.6±0.1)ng/ml,t=3.6,P<0.01;(4.1±0.4)vs(2.1±0.3)ng/ml,t=4.3,P<0.01].In addition,fasting insulin and body weight could be maintained at a low level for a long time on high fat diet[(3.1±0.3)vs(0.7±0.1)ng/ml,t=8.1,P<0.01;(453±11)vs(349±6)g,t=8.5,P<0.01].The mechanism study found that insulin signal pathway of adipose tissue was inhibited(1.0±0.1 vs 0.5±0.1,t=6.4,P<0.01),fatty acid synthesis and decomposition were decreased,and the expression of adenosine monophosphate-activated protein kinase was enhanced(1.0±0.1 vs 1.4±0.1,t=4.0,P<0.01).After the removal of most pancreatic tissues,the levels of fasting plasma insulin and glucagon were reduced 71.7%and 68.0%respectively[(1.10±0.10)vs(0.30±0.04)ng/ml,t=7.5,P<0.01;(16.2±0.8)vs(5.2±0.9)pmol/L,t=9.1,P<0.01],but the fasting blood glucose was not significantly increased,and the body weight was significantly lower in the normal diet and high-fat diet group compared to sham group[(434±13)vs(389±5)g,t=3.1,P<0.05;(548±16)vs(433±11)g,t=6.0,P<0.01].Conclusions RYGB can maintain low body weight and blood glucose homeostasis for a long time by reducing energy intake and avoiding hyperinsulinemia.The mechanism is closely related to the inhibition of fat synthesis and metabolism,and the enhancement of catabolism.