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基于Bcl-2/Bax通路探究芪地降糖汤对2型糖尿病大鼠胰岛细胞凋亡的影响

Effects of Qidi Jiangtang Decoction on pancreatic islet cell apoptosis in a rat model of T2DM via Bcl-2/Bax pathway
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摘要 目的 探究芪地降糖汤对2型糖尿病(T2DM)大鼠胰岛细胞凋亡的作用。方法 SD大鼠随机分为对照组、模型组、二甲双胍组(200 mg/kg)和芪地降糖汤组(7.3 g/kg),采用链脲佐菌素(STZ)结合高脂高糖喂养诱导建立大鼠T2DM模型,给药干预8周。给药结束后,测定大鼠空腹血糖(FBG)、餐后2小时血糖(PG2h)、口服葡萄糖耐量实验的曲线下面积(OGTT-AUC)和体质量;采用生化试剂盒检测大鼠血清中糖化血清蛋白(GSP)、糖化血红蛋白(HbA1c)、丙二醛(MDA)水平和总超氧化物歧化酶(T-SOD)活性;采用ELISA试剂盒检测大鼠血清胰岛素(INS)、C肽(C-P)并计算胰岛素抵抗指数(HOMA-IR);HE染色观察胰岛形态结构变化;TUNEL染色观察胰岛细胞凋亡情况;免疫荧光法检测胰岛cleaved-Caspase-3蛋白表达;Western blot法检测胰腺组织Bcl-2、Bax、cleaved-Caspase-3和Caspase-7蛋白表达;RT-qPCR法检测胰腺组织Bcl-2、Bax和Caspase-3 mRNA表达。结果 与模型组比较,芪地降糖汤组FBG、PG2h、OGTT-AUC、GSP、HbA1c、HOMA-IR和MDA水平降低(P<0.05,P<0.01),体质量、C-P、INS水平和T-SOD活性升高(P<0.05,P<0.01);胰岛形态结构和细胞凋亡程度得到改善;胰腺组织Bcl-2蛋白表达升高(P<0.05),Bax、cleaved-Caspase-3和Caspase-7蛋白表达降低(P<0.05,P<0.01),Bcl-2 mRNA表达升高(P<0.05),Bax和Caspase-3 mRNA表达降低(P<0.05,P<0.01)。结论 芪地降糖汤可通过调节内源性细胞凋亡途径改善胰岛细胞损伤。 AIM To investigate the effects of Qidi Jiangtang Decoction on pancreatic islet cell apoptosis in a rat model of type 2 diabetes mellitus(T2DM).METHODS The SD rats were randomly assigned to the control group,the model group,the metformin group(200 mg/kg),and the Qidi Jiangtang Decoction group(7.3 g/kg).After establishing T2DM rat models via intraperitoneal streptozotocin(STZ)injection combined with a high-fat/high-sugar diet,the drug intervention was administered for 8 weeks.After the intervention period,the following parameters were assessed:fasting blood glucose(FBG),2-hour postprandial blood glucose(PG2h),oral glucose tolerance test area under the curve(OGTT-AUC),and body weight.Biochemical kits were used to measure the levels of glycated serum protein(GSP),glycated hemoglobin(HbA1c),malondialdehyde(MDA),and the activity of total superoxide dismutase(T-SOD)in rat serum.Serum insulin(INS)and C-peptide(C-P)levels were quantified using ELISA kits,and insulin resistance was assessed via the homeostasis model assessment(HOMA-IR).Pancreatic islet morphology and structure were evaluated using hematoxylin and eosin(HE)staining,while TUNEL staining was employed to detect islet cell apoptosis.Immunofluorescence was used to detect the protein expression of cleaved Caspase-3 in islets.Western blot quantified the protein expressions of Bcl-2,Bax,cleaved Caspase-3 and Caspase-7 in pancreatic tissue.Additionally,RT-qPCR was used to analyze mRNA expressions of Bcl-2,Bax,and Caspase-3 in pancreatic tissue.RESULTS Compared to the model group,the Qidi Jiangtang Decoction group exhibited significant metabolic improvements including reduced levels of FBG,PG2h,OGTT-AUC,GSP,HbA1c,HOMA-IR,and MDA(P<0.05,P<0.01);increased body weight,C-P,INS,and T-SOD(P<0.05,P<0.01);enhanced pancreatic function including improved pancreatic islet morphology and reduced apoptosis,upregulated Bcl-2 protein expression(P<0.05);downregulated Bax,cleaved-Caspase-3 and Caspase-7(P<0.05,P<0.01);altered gene expression including increased Bcl-2 mRNA(P<0.05),and decreased Bax and Caspase-3 mRNA(P<0.05,P<0.01).CONCLUSION Qidi Jiangtang Decoction may mitigate pancreatic islet cell injury by regulating the intrinsic apoptosis pathway.
作者 马雷雷 赵英捷 王祎彬 王静雅 田春雨 常宏 喇孝瑾 张碧溦 孟然 李继安 MA Lei-lei;ZHAO Ying-jie;WANG Yi-bin;WANG Jing-ya;TIAN Chun-yu;CHANG Hong;LA Xiao-jin;ZHANG Bi-wei;MENG Ran;LI Ji-an(School of Public Health,North China University of Science and Technology,Tangshan 063210,China;Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications,College of Traditional Chinese Medicine,North China University of Science and Technology,Tangshan 063210,China;Qian’an Hospital of Traditional Chinese Medicine,Tangshan 064400,China;Institute of Coastal Agriculture,Hebei Academy of Agriculture and Forestry Sciences,Tangshan 063200,China)
出处 《中成药》 北大核心 2025年第12期3950-3958,共9页 Chinese Traditional Patent Medicine
基金 国家科学技术部对发展中国家科技援助项目(KY201904005) 河北省自然科学基金资助项目(H2023209038) 河北省重大科技支撑计划项目(24297701Z)。
关键词 芪地降糖汤 2型糖尿病(T2DM) 胰岛细胞 凋亡 氧化应激 Bcl-2/Bax通路 Caspase-3 Qidi Jiangtang Decoction T2DM islet cell apoptosis oxidative stress Bcl-2/Bax pathway Caspase-3
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