藿朴夏苓汤对链脲佐菌素诱导糖尿病大鼠的降血糖作用及机制研究  

Hypoglycemic Effect and Mechanism of Huo Pu Xia Ling Tang on Streptozotocin-induced Diabetic Rats

作　　者：钟艳花 林重 唐东晖 熊艳云[2] 杨俭勤[3] ZHONG Yanhua;LIN Zhong;TANG Donghui;XIONG Yanyun;YANG Jianqin(Liwan Hospital of Traditional Chinese Medicine,Guangzhou 510140 Guangdong,China;Guangzhou Municipal Hospital of Traditional Chinese Medicine,Guangzhou 510130 Guangdong,China;Wangjing Hospital of China Academy of Chinese Medical Sciences,Beijing 100102,China)

机构地区：[1]广州市荔湾区中医医院,广东广州510140 [2]广州市中医医院,广东广州510130 [3]中国中医科学院望京医院,北京100102

出　　处：《中药新药与临床药理》2020年第11期1305-1311,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81302945);广东省中医药管理局科研项目(20201275)。

摘　　要：目的研究藿朴夏苓汤(HPXLT)对链脲佐菌素(STZ)诱导糖尿病大鼠的降血糖作用及机制。方法采用腹腔注射STZ(65 mg·kg^(-1))制备糖尿病大鼠模型。将60只雄性SD大鼠随机分为正常对照组、模型组、格列本脲组(5 mg·kg-1)及藿朴夏苓汤高、中、低剂量组(2、1、0.5 g·kg^(-1)),每日1次,连续灌胃给药4周。测定各组大鼠体质量、摄食量、饮水量;进行糖耐量测定,计算糖耐量下血糖-时间的曲线下峰面积(AUC);生化指标检测:空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)及血清胰岛素水平;采用HE染色观察胰腺组织病理学变化;Western Blot法测定胰腺组织中BCL-2、BAX及胰腺-十二指肠同源异型盒基因-1(PDX-1)蛋白表达水平;Real-time RT-PCR法测定胰腺BCL-2、BAX及PDX-1 mRNA表达水平。结果与正常对照组比较,模型组大鼠的体质量明显降低,而摄食量、饮水量明显增加(P<0.01);FBG值、糖耐量实验的血糖-时间曲线下峰面积(AUC)显著升高(P<0.01);血清中的TC、TG、LDL-c及MDA、NO水平显著升高(P<0.01),HDL-c、GSH、SOD及胰岛素水平显著降低(P<0.01);BAX mRNA及蛋白表达水平显著升高(P<0.01),BCL-2、PDX-1 mRNA及蛋白表达水平显著降低(P<0.01)。与模型组比较,各给药组大鼠的体质量明显增加,摄食量、饮水量明显降低(P<0.01);FBG值、AUC值均明显降低(P<0.05,P<0.01);血清TC、TG、LDL-c及MDA、NO水平明显降低(P<0.05,P<0.01),HDL-c、GSH、SOD及胰岛素水平明显升高(P<0.05,P<0.01);胰腺组织中的BAX mRNA及蛋白表达水平显著降低(P<0.05,P<0.01),而BCL-2、PDX-1 mRNA及蛋白表达水平显著升高(P<0.05,P<0.01)。结论藿朴夏苓汤对STZ诱导的糖尿病大鼠具有降血糖作用,可能与其上调PDX-1的表达,提高抗氧化水平,改善胰岛β细胞功能有关。Objective To study the hypoglycemic effect and mechanism of Huo Pu Xia Ling Tang(HPXLT)on streptozotocin(STZ)-induced diabetic rats.Methods Diabetic rats were induced by intraperitoneal injection of STZ(65 mg·kg-1).Rats were randomly divided into normal control group,model group,HPXLT high,medium and low dose groups(2,1,0.5 g·kg-1),glibenclamide group(5 mg·kg-1)and were administrated once per day by gavage for 4 weeks.Body weight,food intake,water intake and glucose tolerance were measured.The levels of fasting blood glucose(FBG),serum lipids(TC,TG,HDL-c,LDL-c),oxidative stress(GSH,SOD,MDA,NO)and serum insulin were measured by biochemical analysis methods.Pathological changes of pancreas were detected by HE staining;qRT-PCR and Western Blot were used to detect expression levels of BCL-2,BAX and PDX-1 in pancreatic tissue.Results Compared with the normal control group,the body weight of the model group was reduced,the intake of food and drinking water were significantly increased(P<0.01);the levels of FBG,serum TC,TG,LDL-c,MDA and NO were significantly increased(P<0.01),the levels of HDL-c,GSH,SOD and serum insulin were significantly reduced(P<0.01)with statistically significant differences;BAX mRNA and protein levels were significantly elevated(P<0.01).The expression levels of BCL-2 and PDX-1 decreased significantly(P<0.05,P<0.01).Compared with the model group,the body weight of rats in the administration groups were significantly higher(P<0.01),the food intake and drinking water intake were significantly lower(P<0.01);the levels of FBG,serum TC,TG,LDL-C,MDA and NO were significantly lower(P<0.01),while the levels of HDL-C,GSH,SOD and serum insulin were significantly higher(P<0.01);BAX mRNA and the protein levels decreased significantly(P<0.05,P<0.01),while the mRNA and protein expression levels of BCL-2 and PDX-1 increased significantly(P<0.05,P<0.01).Conclusion Huo Pu Xia Ling Tang has hypoglycemic effect,and its mechanism may be related to the activation of PDX-1 expression and the improvement ofβcell apop

关 键 词：藿朴夏苓汤 糖尿病 链脲佐菌素 降血糖 抗氧化 降血脂 胰腺-十二指肠同源异型盒基因-1 胰岛Β细胞 大鼠 

分 类 号：R285.5[医药卫生—中药学]