摘要
目的:探讨苯扎贝特(BEZ)减轻小鼠糖尿病肝病的作用及可能机制。方法:长期高能量饲料联合链脲菌素(STZ)腹腔注射建立糖尿病肝病模型,给予BEZ(75 mg·kg-1·d-1)灌胃4周。每周监测空腹血糖(FBG);HE染色观察肝脏形态学改变,生化试剂盒检测小鼠肝功能(丙氨酸氨基转移酶和天门冬氨酸氨基转移酶)、血脂(总胆固醇和甘油三酯)、胰岛素(INS)和糖化血红蛋白(HbA1c)水平,计算胰岛素抵抗指数(HOMA-IR)。RT-qPCR和Western blot方法检测肝脏过氧化物酶体增殖激活受体(PPARs)的mRNA和蛋白表达。结果:给予STZ 7 d后,小鼠FBG水平持续>11.1 mmol/L。实验结束时模型组小鼠INS、HbA1c及HOME-IR均明显增加(P<0.01),血脂升高(P<0.01);肝功能指标升高(P<0.01),病理检查见肝细胞脂肪变性及炎症细胞浸润;肝脏PPARs的mRNA和蛋白表达明显下降(P<0.01)。BEZ给药明显减轻模型小鼠肝脏损害(P<0.01),降低血糖相关指标和血脂水平(P<0.05),上调PPARs的mRNA和蛋白表达(P<0.01)。结论:BEZ减轻小鼠糖尿病肝损伤,该作用可能与其激活PPARs有关。
AIM: To investigate the effects of bezafibrate(BEZ) on diabetic hepatopathy in mice. ME-THODS: Diabetic hepatopathy model was established by a long-high-energy diet combined with streptozotocin(40 mg·kg-1·d-1× 5 d, ip),and then bezafibrate(75 mg·kg-1·d-1, ig) was supplemented for 4 weeks. Fasting blood glucose(FBG) was detected every week. The structure of liver was observed by HE staining, and the liver function was measured by observing the levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST). Total cholesterol(TC), triglyceride(TG), insulin and HbA1 c were determined by commercial kits, and then HOMA insulin resistance index(HOMA-IR) was calculated. The expression of peroxisome proliferator-activated receports(PPARs) at mRNA and protein levels was determined by RT-qPCR and Western blot, respectively. RESULTS: After 7 days of treatment with streptozotocin, the FBG level of the mice exceeded 11.1 mmol/L. At the end of the experiment, the structural deformation of the hepatocytes(containing abundant fat vacuoles, infiltrated by inflammatory cells, etc.) was observed, with the increases in insulin, HbA1 c, HOMA-IR, TC, TG, ALT and AST in diabetic mice(P<0.01). Meanwhile, the expression of PPARα, PPARβ and PPARγ at mRNA and protein levels was decreased(P<0.01). Bezafibrate treatment markedly attenuated the structural and functional damages of the liver in the diabetic mice(P<0.01), and reduced the levels of FBG, insulin, HbA1 c, HOMA-IR, TC and TG(P<0.05). Bezafibrate also up-regulated the expression of PPARα, PPARβ and PPARγ(P<0.01). CONCLUSION: Bezafibrate attenuates hepatic injury in diabetic mice via the activation of PPARs-related signaling pathway.
作者
吴堃
蒋青松
任凯强
黄波
邱红梅
韩萍
WU Kun;JIANG Qing-song;REN Kai-qiang;HUANG Bo;QIU Hong-mei;HAN Ping(Department of Hepatobiliary Surgery,Chongqing General Hospital,Chongqing 400013,China;Department of Pharmacology,Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology,Chongqing Medical University,Chongqing 400016,China;Department of Pharmacy,Chongqing Yongchuan People’s Hospital,Chongqing 402160,China;Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi 563003,China;Department of Oncology,Chongqing General Hospital,Chongqing 400013,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2020年第3期519-524,共6页
Chinese Journal of Pathophysiology
基金
重庆市渝中区科技计划项目(No.20160127)
重庆市自然科学基金资助项目(No.cstc2017jc jAX0211)
遵义市科技局科学技术联合资金资助项目([2018]31号)。
