胃袖状切除术改善2 型糖尿病小鼠脂肪组织胰岛素抵抗机制研究

Effect of sleeve gastrectomy on insulin resistance in adipose tissue of obesity-associated type 2 diabetes (+db/+db) mice

摘要:

目的 探讨胃袖状切除术（SG）对2 型糖尿病小鼠脂肪组织微囊蛋白1（caveolin -1）表达及胰岛素抵抗的影响。方法 实验于2015 年1 ～ 6 月在中国医科大学附属盛京医院中心实验室进行。选择30只肥胖2 型糖尿病小鼠（+db/+db，C57BL/KsJ）为研究对象，按体重随机等分为3 组：db/db 组（无处理）、db/db-SG 组（行SG）、db/db-sham 组（假手术），每组10 只。术前3 d 和术后7、14、21 及28 d 测定动物体重及每100 g 体重摄食量。术前5 d 和术后30 d，测定小鼠空腹血糖（FBG）及口服葡萄糖耐量（OGTT），ELISA 检测血浆胰岛素、三酰甘油（TG）、胆固醇（TC）、低密度脂蛋白（LDL）；Western blot 和实时聚合酶链反应（Real-time PCR）检测内脏脂肪组织caveolin-1、GLUT4 蛋白及mRNA 表达。结果 db/db-SG组小鼠术后体重、摄食量、空腹血糖、OGTT 曲线下面积、胰岛素抵抗指数与db/db 组及db/db-sham 组比较，差异有统计学意义（P <0.05），db/db-SG 组小鼠术后体重及摄食量降低，空腹血糖下降，OGTT 曲线下面积减少，胰岛素抵抗指数下降；db/db-SG 组血清TG、TC、LDL 水平与db/db 组及db/db-sham 组比较，差异有统计学意义（P <0.05），db/db-SG 组小鼠下降；db/db-SG 组小鼠脂肪组织caveolin-1、GLUT4 蛋白和mRNA 表达与db/db 组及db/db-sham 组比较，差异有统计学意义（P <0.05），均升高。结论 SG 可在术后短期内有效降低2 型糖尿病小鼠体重及摄食量，降低TG、TC，改善胰岛素抵抗，可能与脂肪组织caveolin-1及GLUT4 水平下降有关。

Abstract:

Objective To observe the effect of sleeve gastrectomy (SG) on the expression of caveolin-1 in adipose tissue and insulin resistance status. Methods Thirty 10-week old obesity-associated type 2 diabetes (+db/+db) (C57BL/KsJ) mice were randomly allocated to db/db-SG group, db/db-sham group and db/db blank control group, each group had 10 rats. Body weight and food intake were recorded 3 d before operation and 7, 14, 21 and 28 d after operation. On the 5th d before operation and the 30th d after operation, FBG and OGTT were detected before and after operation; ELISA was used to detect the plasma insulin, TG, TC and LDL; RT-PCR and Western blot were used to detect the expressions of caveolin-1 and GLUT4 in the viceral adipose tissue. Results Compared with the db/db-sham group and the blank control group, the mice in the SG group showed obviously-reduced body weight and food intake (P < 0.05), apparent downward trends of FBG level, AUC of OGTT, and HOMA-IR (P < 0.05). The plasma TC, TG and LDL levels in the SG group decreased as well (P < 0.05). The expressions of caveolin-1 and GLUT4 protein and mRNA in the viceral adipose tissue significantly increased in the SG group compared to the db/db-sham group and the blank control group (P < 0.05). Conclusions SG can significantly lower the body weight and food intake, decrease the plasma TC, TG and LDL, and alleviate the insulin resistance status in a short period after surgery, which may be related to reduced expression of caveolin-1 and GLUT4 in the adipose tissue.