| Abstract: | AIM: To investigate the effects of bezafibrate (BEZ) on diabetic hepatopathy in mice. METHODS: 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 HbA1c 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, HbA1c, 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, HbA1c, 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. |
