西格列汀抑制糖尿病肾病大鼠肾组织的细胞凋亡和炎症  

Sitagliptin inhibits cell apoptosis and inflammation of renal tissues in diabetic nephropathy model rats

作　　者：徐灵芝 任跃忠[1] XU Lingzhi;REN Yuezhong(Department of Endocrinology, Second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310012;Department of Endocrinology, Taizhou Municipal Hospital, Taizhou 318000, China)

机构地区：[1]浙江大学医学院附属第二医院内分泌科,浙江杭州310012 [2]台州市立医院内分泌科,浙江台州318000

出　　处：《细胞与分子免疫学杂志》2019年第3期217-222,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：浙江省自然科学基金(LY16H070006)

摘　　要：目的研究二肽基肽酶4(DPP-4)抑制剂西格列汀处理糖尿病肾病大鼠后,凋亡相关因子的表达趋势。方法 ZDF模型鼠(fa/fa)随机分为糖尿病组和西格列汀处理组,以ZDF对照鼠(fa/^+)为对照组。葡萄糖氧化酶试剂盒测定血清非空腹血糖水平, ELISA小鼠尿微量白蛋白检测试剂盒检测尿蛋白水平,全自动生化分析仪检测血液生化指标;实时荧光定量PCR检测肾组织肿瘤坏死因子受体1(TNFR1)、 Fas、胱天蛋白酶3(caspase-3)的mRNA水平, Western blot法检测DPP-4、高血糖素样肽1(GLP-1)、 TNFR1、 caspase-3和caspase-8蛋白水平。结果糖尿病组大鼠血糖、尿微量白蛋白、血尿素氮、血清肌酐水平增加,西格列汀处理后,相关指标水平显著降低;糖尿病组大鼠TNFR1、 caspase-3 mRNA水平增加,西格列汀处理组后降低;糖尿病组大鼠DPP-4、 TNFR1、 caspase-3、 caspase-8蛋白水平增加、 GLP-1蛋白水平降低,西格列汀处理后相应蛋白含量出现相反变化。结论西格列汀抑制糖尿病肾病大鼠的炎症和细胞凋亡。Objective To investigate the expression of apoptosis-related factors in diabetic nephropathy model rats after the intervention of dipeptidyl peptidase 4(DPP-4) inhibitor sitagliptin. Methods ZDF(fa/fa) and ZDF(fa/^+) rats were randomly divided into diabetes mellitus group and sitagliptin treatment group, and ZDF control mice(fa/^+) were used as the control group. Non-fasting blood glucose levels were measured with glucose oxidase kit. Urine albumin level was detected by ELISA, and blood biochemical indexes were detected by automatic biochemical analyzer. The mRNA levels of tumor necrosis factor receptor 1(TNFR1), Fas, and caspase-3 in the renal tissue were examined by real-time fluorescence quantitative PCR, and the protein levels of DPP-4, GLP-1, TNFR1, caspase-3, and caspase-8 were detected by Western blot analysis. Results The levels of blood glucose, urinary microalbumin, blood urea nitrogen, serum creatinine increased in the diabetic group, and the levels of related indicators significantly decreased after treatment with sitagliptin. The mRNA levels of TNFR1 and caspase-3 in the diabetic rats went up and then down after the treatment with sitagliptin. The levels of DPP-4, TNFR1, caspase-3 and caspase-8 in the diabetic rats increased, while the level of GLP-1 decreased;after the treatment with sitagliptin, the corresponding protein content showed opposite changes. Conclusion Sitagliptin can inhibit inflammation and apoptosis in rats with diabetic nephropathy.

关 键 词：糖尿病肾病 二肽基肽酶4(DPP-4) 胰高血糖素样肽1(GLP-1) 肿瘤坏死因子受体1(TNFR1) Fas 胱天蛋白酶3(caspase-3) 

分 类 号：R392-33[医药卫生—免疫学] R587.1[医药卫生—基础医学]