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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
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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 of lipid deposition due to inflammatory infiltration.The pathological changes of group C were more serious than that of group B.The above pathological changes of rats in group D were less than those in group C.The protein expressions of GRP78 and Caspase-12 in group D were significantly lower than those in group C(P<0.05).Conclusion:SG surgery can reduce the body weight and blood glucose level in obese rats with T2DM model,improve glucose and lipid metabolism,reduce insulin resistance,and alleviate pancreatic injury,which may be related to inhibiting the activation of GRP78/Caspase-12 pathway.
作者 孟令凯 李大勇 王宁 王桂明 张炳南 李若彤 潘立峰 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)
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)。
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 Sleeve Gastrectomy Obesity Type2Diabetes Mellitus Glycolipid Metabolism Pancreatic Injury GRP78/Caspase-12 Pathway
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