胃旁路术治疗2型糖尿病的作用机制

目的 探讨胃旁路术治疗2型糖尿病大鼠的作用机制.方法 将72只8周龄的GK大鼠按照随机数字表法分为手术组、假手术组、饮食控制组和对照组,每组18只.手术组大鼠施行胃旁路术,假手术组大鼠施行离断胃窦十二指肠原位吻合术,饮食控制组大鼠按15 g/d控制每只大鼠进食量,对照组大鼠自由进食.术前、术后第2、4、8周检测各组大鼠空腹、餐后血糖和胰高血糖素样肽-1(GLP-1).术后第2、4、8周检测各组大鼠餐后血糖和GLP-1后处死大鼠(每组6只),取出胰腺组织采用TUNEL法检测胰岛β细胞凋亡情况.采用t检验分析数据.结果 手术组大鼠术前空腹和餐后血糖分别为(16.2±0.8)mmol/L和(31.1±1.1)mmol/L,术后第4、8周逐渐降低为(9.2±0.6)mmol/L和(13.1±0.7)mmol/L、(9.7±0.7)mmol/L和(12.3±0.7)mmol/L,手术前后比较,差异有统计学意义(t=20.7、49.7,18.8、39.0,P<0.05).手术组大鼠术后第4、8周空腹和餐后血糖水平明显低于同时相点的假手术组、饮食控制组和对照组(t=27.7、-57.8,11.3、-59.9,-27.4、-48.2,-13.2、-52.7,-7.0、-24.9,-18.2、-56.4,P<0.05).手术组大鼠术前空腹和餐后GLP-1分别为(10.7±1.0)pmol/L和(42.5±1.2)pmol/L,术后第4、8周逐渐升高为(26.1±0.9)pmol/L和(90.7±1.7)pmol/L、(25.3±1.2)pmol/L和(90.4±2.0)pmol/L,手术前后比较,差异有统计学意义(t=-42.1、-92.4,-29.1、-72.7,P<0.05).手术组大鼠术后第4、8周空腹和餐后GLP-1水平明显高于同时相点的假手术组、饮食控制组和对照组(t=48.0、61.9,38.0、62.2,50.9、65.2,37.0、48.1,27.5、51.6,17.5,52.9,P<0.05).手术组大鼠胰岛随着术后时间的延长,凋亡细胞数逐渐减少,细胞凋亡率明显降低.手术组、假手术组、饮食控制组和对照组术后第4、8周细胞凋亡率分别为5.9%±0.7%、47.2%±1.0%、21.1%±1.2%、46.5%±1.4%和6.3%±1.1%、47.2%±1.0%、21.2%±1.2%、46.0%±1.4%,手术组细胞凋亡率较同时相点的假手术组、饮食控制组、对照组明显降低(t=-82.2、-67.0,-27.1、-22.4,-55.2、-54.6,P<0.05).结论 胃旁路手术后2型糖尿病大鼠血糖降低,GLP-1分泌明显增加,可以显著抑制胰岛β细胞凋亡.

Abstract：

Objective To investigate the mechanism of gastric bypass surgery in the treatment of type 2 diabetes mellitus in a rat model. Methods Seventy-two 8-week-old GK rats were randomly divided into operation group, sham operation group, diet control group and control group (18 rats in each group) according to the random number table. Rats in the operation group and the sham operation group received gastric bypass surgery and transection and reanastomosis of the gastrointestinal tract, respectively. The food intake was set as 15 g/d for each rat in the diet control group, while rats in the control group were fed ad libitum. The levels of fasting blood glucose ( FBG), postprandial blood glucose (PPBG) and glucagon-like peptide-1 (GLP-1) were detected before operation and at postoperative week 2, 4 and 8. The levels of PPBG and GLP-1 were detected at postoperative week 2, 4 and 8, then 6 rats of each group were sacrificed to detect the apoptosis of islet B cells using the TUNEL method. All data were analyzed using the t test. Results In the operation group, the preoperative levels of FBG and PPBG were (16.2±0.8)mmol/L and (31.1 ± 1. L)mmol/L, respectively, which were significantly higher than (9.2± 0.6) mmol/L and (13.1 ±0.7) mmol/L at 4 weeks after the operation, and (9. 7 ± 0. 7) mmol/L and (12. 3 ± 0.7) mmol/L at 8 weeks after the operation (t = 20. 7, 49. 7; 18. 8, 39. 0, P < 0.05 ). The levels of FBG and PPBG before the operation and at 4 and 8 weeks after the operation in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = 27.7, -57.8; 11.3, -59.9; -27.4, -48.2; -13.2, -52.7; -7.0, -24.9; -18.2, -56.4, P<0.05). In the operation group, the levels of fasting GLP-1 and postprandial GLP-1 were ( 10. 7 ± 1. 0) pmol/L and (42.5 ±1.2)pmol/L, respectively, which were significantly lower than (26. 1 ±0.9)pmol/L and (90.7 ± 1.7)pmol/L at4 weeks after the operation, and (25.3 ± 1.2)pmol/L and (90.4 ±2.0)pmol/L at 8 weeks after the operation (t=42.1, -92.4; -29.1, -72.7, P <0.05). The levels of fasting GLP-1 and postprandial GLP-1 before the operation and at 4 and 8 weeks after the peration in the operation group were significantly higher than those in the sham operation group, diet control group and control group at corresponding time points (t = 48.0, 61.9; 38.0, 62.2; 50.9, 65.2; 37.0, 48. 1; 27.5, 51.6; 17.5, 52.9, P<0.05). The number of the apoptotic islet β cells in the operation group was decreased with time. The apoptosis rates in the operation group, sham operation group, diet control group and control group were 5.9%±0.7% , 47.2%± 1.0% , 21. 1%± 1. 2% , 46.5%±1.4% at 4 weeks after the operation, and 6.3%±1. 1% , 47.2%±1.0% , 21.2%±1.2% and 46.0% ± 1.4% at 8 weeks after the operation. The apoptosis rates in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = -82. 2, - 67. 0; - 27. 1, - 22. 4; - 55. 2, - 54. 6, P < 0.05). Conclusion After gastric bypass surgery, the level of blood glucose reduces and the level of GLP-1 increases which significantly inhibit the apoptosis of islet B cells in rats with type 2 diabetes mellitus.

Mechanism of gastric bypass surgery in the treatment of type 2 diabetes mellitus in a rat model

Objective To investigate the mechanism of gastric bypass surgery in the treatment of type 2 diabetes mellitus in a rat model. Methods Seventy-two 8-week-old GK rats were randomly divided into operation group, sham operation group, diet control group and control group (18 rats in each group) according to the random number table. Rats in the operation group and the sham operation group received gastric bypass surgery and transection and reanastomosis of the gastrointestinal tract, respectively. The food intake was set as 15 g/d for each rat in the diet control group, while rats in the control group were fed ad libitum. The levels of fasting blood glucose ( FBG), postprandial blood glucose (PPBG) and glucagon-like peptide-1 (GLP-1) were detected before operation and at postoperative week 2, 4 and 8. The levels of PPBG and GLP-1 were detected at postoperative week 2, 4 and 8, then 6 rats of each group were sacrificed to detect the apoptosis of islet B cells using the TUNEL method. All data were analyzed using the t test. Results In the operation group, the preoperative levels of FBG and PPBG were (16.2±0.8)mmol/L and (31.1 ± 1. L)mmol/L, respectively, which were significantly higher than (9.2± 0.6) mmol/L and (13.1 ±0.7) mmol/L at 4 weeks after the operation, and (9. 7 ± 0. 7) mmol/L and (12. 3 ± 0.7) mmol/L at 8 weeks after the operation (t = 20. 7, 49. 7; 18. 8, 39. 0, P < 0.05 ). The levels of FBG and PPBG before the operation and at 4 and 8 weeks after the operation in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = 27.7, -57.8; 11.3, -59.9; -27.4, -48.2; -13.2, -52.7; -7.0, -24.9; -18.2, -56.4, P<0.05). In the operation group, the levels of fasting GLP-1 and postprandial GLP-1 were ( 10. 7 ± 1. 0) pmol/L and (42.5 ±1.2)pmol/L, respectively, which were significantly lower than (26. 1 ±0.9)pmol/L and (90.7 ± 1.7)pmol/L at4 weeks after the operation, and (25.3 ± 1.2)pmol/L and (90.4 ±2.0)pmol/L at 8 weeks after the operation (t=42.1, -92.4; -29.1, -72.7, P <0.05). The levels of fasting GLP-1 and postprandial GLP-1 before the operation and at 4 and 8 weeks after the peration in the operation group were significantly higher than those in the sham operation group, diet control group and control group at corresponding time points (t = 48.0, 61.9; 38.0, 62.2; 50.9, 65.2; 37.0, 48. 1; 27.5, 51.6; 17.5, 52.9, P<0.05). The number of the apoptotic islet β cells in the operation group was decreased with time. The apoptosis rates in the operation group, sham operation group, diet control group and control group were 5.9%±0.7% , 47.2%± 1.0% , 21. 1%± 1. 2% , 46.5%±1.4% at 4 weeks after the operation, and 6.3%±1. 1% , 47.2%±1.0% , 21.2%±1.2% and 46.0% ± 1.4% at 8 weeks after the operation. The apoptosis rates in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = -82. 2, - 67. 0; - 27. 1, - 22. 4; - 55. 2, - 54. 6, P < 0.05). Conclusion After gastric bypass surgery, the level of blood glucose reduces and the level of GLP-1 increases which significantly inhibit the apoptosis of islet B cells in rats with type 2 diabetes mellitus.