PPARs signaling pathway is involved in diabetic hepatopathy in mice / 中国病理生理杂志

ABSTRACT

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 for 4 weeks combined with intraperitoneal injection of streptozotocin(STZ;40 mg· kg-1· d-1for 5 d). 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 another 4 weeks.Mo-reover,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 for 7 d,the FBG of mice exceeded 11.1 mmol/L,suggesting that the diabetic model was established. After 4 weeks,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, com-pared with the control group,the mRNA and protein expression of PPARα,PPARβand PPARγdecreased,but the expres-sion of nuclear factor-κB(NF-κB),cyclooxygenase 2(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 in-duced by long-term high-energy diet feeding combined with intraperitoneal injection of STZ.