Roux-en-Y胃旁路术对2型糖尿病大鼠肝脏胆汁酸信号及糖异生的影响  

Effect of Roux-en-Y gastric bypass on the hepatic bile acids signaling and gluconeogenesis in type 2 diabetic rats

作　　者：常诚 王百林[1] 苑伟 方少梅[1] 洪劲松[1] 颜勇 Chang Cheng;Wang Bailin;Yuan Wei;Fang Shaomei;Hong Jinsong;Yan Yong(Department of General Surgery,Guangzhou Red Cross Hospital,Medical College,Jinan University,Guangzhou 510220,China)

机构地区：[1]暨南大学医学院附属广州红十字会医院普外科,510220

出　　处：《中华实验外科杂志》2021年第3期446-448,共3页Chinese Journal of Experimental Surgery

基　　金：广州市卫生和计划生育科技项目(20181A011027);广东省医学科学技术研究基金项目(201711221446275)。

摘　　要：目的探讨Roux-en-Y胃旁路术(RYGB)对2型糖尿病(T2DM)大鼠肝脏胆汁酸信号及糖异生的影响。方法将16只健康雄性Sprague-Dawley大鼠通过高脂饲料喂养并腹腔注射链脲佐菌素诱导T2DM,随机数字表法分为假手术组(n=8)和手术组(n=8)。手术组行RYGB术,假手术组在与手术组相同位置行胃肠横断并原位吻合。术前及术后第1、2、4、6、8周测各组摄食量和空腹血糖;术前、术后2、8周行口服葡萄糖耐量试验(OGTT)及胰岛素敏感试验(ITT);术后8周留取空腹血清检测总胆汁酸水平,留取肝脏组织用反转录聚合酶链反应检测法尼醇X受体(FXR)、小异二聚体伴侣(SHP)、磷酸烯醇式丙酮酸羧激酶(PEPCK)和葡萄糖-6-磷酸酶(G6Pase)mRNA表达水平,应用SPSS 20.0软件进行统计分析,组间比较采用t检验。结果手术组术后第4、6、8周摄食量[(18±2)、(19±3)、(20±4)g/d]显著低于假手术组[(24±3)、(28±4)、(26±3)g/d],手术组术后第2、4、6、8周空腹血糖[(6.9±0.9)、(6.0±1.1)、(6.4±0.8)、(6.8±0.7)mmol/L]显著低于假手术组[(12.9±1.4)、(10.8±0.8)、(9.4±1.1)、(9.0±1.0)mmol/L],差异有统计学意义(t=4.707、5.091、3.394、9.209、9.982、6.239、5.098,P<0.05);术后2周,手术组OGTT、ITT曲线下面积[(898±118)、(428±85)mmol/(L·min)]显著低于假手术组[(1508±108)、(788±98)mmol/(L·min)],术后8周,手术组OGTT、ITT曲线下面积[(975±102)、(455±76)mmol/(L·min)]显著低于假手术组[(1575±96)、(775±86)mmol/(L·min)],差异有统计学意义(t=10.790、7.849、12.120、7.886,P<0.05);术后8周,手术组大鼠血清总胆汁酸[(105.17±14.81)μmol/L]显著高于假手术组[(68.87±10.81)μmol/L],差异有统计学意义(t=5.600,P<0.05);手术组与假手术组比较,肝脏FXR和SHP mRNA的表达显著上调(1.67±0.31比1.17±0.11、2.37±0.21比1.33±0.18),PEPCK和G6Pase mRNA的表达显著下调(0.77±0.12比1.15±0.14、0.87±0.08比1.05±0.10),差异有统计学意义(t=4.299、10.640、5.829、3.9Objective To investigate the effect of Roux-en-Y gastric bypass(RYGB)on the hepatic bile acids signaling and gluconeogenesis in type 2 diabetes mellitus(T2DM)rats.Methods A total of 16 Sprague-Dawley male rats were fed on a high-fat diet and injected intraperitoneally with streptozotocin to induce T2DM,then all rats were randomly divided into sham surgery group(n=8)and RYGB group(n=8).RYGB surgery was performed in RYGB group,sham surgeries involved the same gastrointestinal transections as those in the RYGB group,and re-anastomosis was performed at the same sites.Fasting blood glucose levels and food intake were measured before and 1st,2nd,4th,6th,8th week after surgery.Oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were performed preoperatively and at 2nd and 8th week postoperatively.At 8th week postoperatively,the fasting serum bile acids levels were measured and hepatic tissues were taken to compare the mRNA expression of farnesoid X receptor(FXR),small heterodimeric partner(SHP),phosphoenolpyruvate carboxykinase(PEPCK)and glucose-6-phosphatase(G6Pase)by reverse transcriptase-polymerase chain reaction.Results At 4th,6th,8th week postoperatively,the food intake in RYGB group[(18±2),(19±3),(20±4)g/d]was decreased as compared with sham surgery group[(24±3),(28±4),(26±3)g/d];At 2nd,4th,6th and 8th week postoperatively,the fasting blood glucose levels in RYGB group[(6.9±0.9),(6.0±1.1),(6.4±0.8),(6.8±0.7)mmol/L]were decreased as compared with sham surgery group[(12.9±1.4),(10.8±0.8),(9.4±1.1),(9.0±1.0)mmol/L],with significant differences(t=4.707,5.091,3.394,9.209,9.982,6.239,5.098,P<0.05);On postoperative week 2,the areas under the curve of OGTT and ITT in RYGB group[(898±118),(428±85)mmol/(L·min)]were decreased compared with sham surgery group[(1508±108),(788±98)mmol/(L·min)];On postoperative week 8,the areas under the curve of OGTT and ITT in RYGB group[(975±102),(455±76)mmol/(L·min)]were decreased as compared with sham surgery group[(1575±96),(775±86)mmol/(L·min)],with s

关 键 词：2型糖尿病 胆汁酸 糖异生 

分 类 号：R656.61[医药卫生—外科学] R587.1[医药卫生—临床医学]