袖状胃切除术对肥胖伴2型糖尿病大鼠的作用及机制研究  

Effect and mechanism of sleeve gastrectomy on obese rats with type 2 diabetes mellitus

作　　者：孟令凯[1] 李大勇[1] 王宁[1] 王桂明 张炳南[1] 李若彤 潘立峰[1] Meng Lingkai;Li Dayong;Wang Ning;Wang Guiming;Zhang Bingnan;Li Ruotong;Pan Lifeng(Department of General Surgery,NHC Key Laboratory of Hormones and Development,Tianjin Key Laboratory of Metabolic Diseases,Chu Hsien-I Memorial Hospital&Tianjin Institute of Endocrinology,Tianjin Medical University,Tianjin 300134,China)

机构地区：[1]天津医科大学朱宪彝纪念医院普外科,天津市内分泌研究所,国家卫健委激素与发育重点实验室,天津市代谢性疾病重点实验室,天津300134

出　　处：《中华普外科手术学杂志（电子版）》2024年第6期638-642,共5页Chinese Journal of Operative Procedures of General Surgery(Electronic Edition)

基　　金：天津市教委科研计划项目(自然科学)课题(2022KJ213)。

摘　　要：目的研究袖状胃切除术(SG)对肥胖伴2型糖尿病(T2DM)大鼠的作用及可能机制。方法选取60只大鼠随机均分为正常对照组(A组,n=15只)、单纯肥胖组(B组,n=15只)、肥胖伴2型糖尿病组(C组,n=15只)及袖状胃切除术组(D组,n=15只),分别进行相应造模及干预8周。采用SPSS 22.0统计学软件进行数据分析。大鼠空腹血糖(FBG)、胰岛素抵抗指数(HOMA-IR)、葡萄糖耐量试验(OGTT)曲线下面积(AUC)、脂代谢指标[总胆固醇(TC)、三酰甘油(TG)]、炎症指标[C反应蛋白(CRP)、白细胞介素6(IL-6)]、血清淀粉酶(AMY)水平及胰腺组织中葡萄糖调节蛋白78(GRP78)和半胱氨酸蛋白水解酶-12(Caspase-12)蛋白表达等实验数据均采用(χ±s)表示,多组间比较采用One-Way ANOVA分析,LSD检验行组间两两比较。P<0.05为差异有统计学意义。结果仅D组术后3只大鼠死亡,其余均建模成功。术前,B、C、D组大鼠体重较A组明显升高(P<0.05),C、D组FBG水平及OGTT_(AUC)值明显高于A、B组(P<0.05);术后2~8周,B组大鼠体重高于A组(P<0.05),D组体重及FBG水平低于C组(P<0.05);术后8周时,D组大鼠OGTT AUC值及HOME-IR指数明显低于C组(P<0.05)。D组TG水平及CRP、IL-6、AMY水平明显低于C组(均P<0.05)。相比A组,B、C组大鼠胰岛细胞形态不规则且排列紊乱,细胞边界模糊不清,胰岛间质中有空泡出现,可见炎症浸润就脂质沉积出现,C组病理改变较B组加重;D组大鼠上述病理改变较C组减轻。D组大鼠GRP78、Caspase-12蛋白表达明显低于C组(P<0.05)。结论SG手术能够降低肥胖伴T2DM模型大鼠的体重及血糖水平,改善糖脂代谢,降低胰岛素抵抗,减轻胰腺损伤,可能与抑制GRP78/Caspase-12通路活化相关。Objective To study the effect and possible mechanism of sleeve gastrectomy(SG)on obese rats with type 2 diabetes mellitus(T2DM).Methods A total of 60 rats were randomly divided into normal control group(group A,n=15),simple obesity group(group B,n=15),obesity group with type 2 diabetes mellitus(group C,n=15)and sleeve gastrectomy group(group D,n=15).The rats underwent corresponding modeling and intervention for 8 weeks,respectively.SPSS 22.0 statistical software was used for data analysis.Fasting blood glucose(FBG),insulin resistance index(HOMA-IR),area under the curve of glucose tolerance test(OGTT)(AUC),lipid metabolism indexes[total cholesterol(TC),triacylglycerol(TG)],inflammation indexes[C-reactive protein(CRP),interleukin-6(IL-6)]and serum amylase(AMY)levels in rats The experimental data of glucose-regulated protein 78(GRP78)and cysteine proteolytic enzyme 12(Caspase-12)in pancreatic tissue were expressed by(χ±s).The multi-group comparison was performed by one-way ANOVA analysis,and the comparison between groups was performed by LSD test.P<0.05 was considered statistically significant.Results Only 3 rats in group D died after operation,and the rest were successfully modeled.Before operation,the body weight of rats in groups B,C and D was significantly higher than that in group A(P<0.05),and the FBG level and OGTTAUC value in groups C and D were significantly higher than those in groups A and B(P<0.05).After 2 to 8 weeks,the body weight of group B was higher than that of group A(P<0.05),and the body weight and FBG level of group D were lower than that of group C(P<0.05).At 8 weeks after operation,the OGTT AUC and HOME-IR index of rats in group D were significantly lower than those in group C(P<0.05).The levels of TG,CRP,IL-6 and AMY in group D were significantly lower than those in group C(all P<0.05).Compared with group A,the islet cells of group B and group C were irregular and disordered,the cell boundaries were blurred,and there were empty vesicles in the interstitial of islets,indicating the presence

关 键 词：袖状胃切除术 肥胖 2型糖尿病 糖脂代谢 胰腺损伤 GRP78/Caspase-12通路 

分 类 号：R656.61[医药卫生—外科学]