摘要
目的:探讨过氧化物酶体增殖物激活受体(PPARs)及炎症相关信号通路在糖尿病肝病中的作用。方法:高能量饲料喂养联合多次腹腔注射小剂量链脲菌素(STZ;40 mg·kg^(-1)·d^(-1),5 d)诱导糖尿病形成后,继续喂养4周,HE染色观察肝脏形态学改变;检测代表小鼠肝功能的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和碱性磷酸酶(ALP)的变化;检测空腹血糖(FBG)、血清总胆固醇(TC)、血清甘油三酯(TG)及血清胰岛素水平(INS),并计算胰岛素抵抗指数(HOMA-IR);利用q PCR和Western blot分别检测PPARs和炎症相关信号通路中相关m RNA及蛋白表达。结果:给予STZ 7 d后,小鼠FBG持续>11.1 mmol/L,糖尿病形成。4周后,实验结束时血清胰岛素水平及HOMA-IR均明显增加(P<0.01),血脂升高(P<0.01),ALT和AST亦显著增加(P<0.01),病理检查见肝细胞脂肪变性及炎性细胞浸润,提示糖尿病小鼠出现肝损伤。与正常对照组相比,糖尿病肝损伤小鼠肝脏PPARα、PPARβ及PPARγ的mRNA和蛋白表达均明显下调(P<0.01),核因子κB(NF-κB)、环氧合酶2(COX-2)和诱导型一氧化氮合酶(i NOS)的表达则明显上调(P<0.01)。结论:PPARs下调及NF-κB-COX-2/i NOS信号通路激活可能与糖尿病肝损伤的发生发展有关。
AIM:To investigate the role of peroxisome proliferator-activated receptors(PPARs)-inflammation signaling pathways in diabetic hepatopathy.METHODS:Diabetic mouse model was established by feeding the mice with a high-energy diet for4weeks combined with intraperitoneal injection of streptozotocin(STZ;40mg·kg-1·d-1for5d).The hepatopathy model was confirmed by histopathological observation and the indexes of liver function,such as alanine aminotransferase(ALT),aspartate aminotransferase(AST)and alkaline phosphatase(ALP),after another4weeks.Moreover,fasting blood glucose(FBG),and serum levels of total cholesterol(TC),triglyceride(TG)and insulin were measured,and the HOMA insulin resistance index(HOMA-IR)was calculated.The mRNA and protein expression levels of PPARs and inflammation-related factors were measured by qPCR and Western blot,respectively.RESULTS:After treatment with STZ for7d,the FBG of mice exceeded11.1mmol/L,suggesting that the diabetic model was established.After4weeks,the structural deformation of the hepatocytes(including hepatocytes containing abundant fat vacuoles,and inflammatory cell infiltration),and the increases in the serum levels of insulin,HOMA-IR,TC,TG,ALT,AST and ALP were observed(P<0.01),indicating the occurrence and progression of hepatopathy in diabetic mice.Meanwhile,compared with the control group,the mRNA and protein expression of PPARα,PPARβand PPARγdecreased,but the expression of nuclear factor-κB(NF-κB),cyclooxygenase2(COX-2)and inducible nitric oxide synthase(iNOS)significantly increased in the diabetic hepatopathy mice(P<0.01).CONCLUSION:Down-regulation of PPARα,PPARβand PPARγand activation of NF-κB-COX-2/iNOS signaling pathways may be involved in the diabetic hepatopathy in mice induced by long-term high-energy diet feeding combined with intraperitoneal injection of STZ.
作者
任凯强
薛莱
黄波
潘文靖
吴堃
蒋青松
REN Kai-qiang;XUE Lai;HUANG Bo;PAN Wen-jing;WU Kun;JIANG Qing-song(Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016,China;Department of Clinical Pharmacy, Jiangyou People’s Hospital, Jiangyou 621700,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 Hepatobi- liary Surgery, Chongqing General Hospital, Chongqing 400013,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第3期555-560,共6页
Chinese Journal of Pathophysiology
基金
重庆市渝中区科技计划项目(No.20160127)
重庆医科大学大学生科学研究与创新实验项目(No.201653)
