Abstract:Objective To establish a rat model of type 2 diabetes mellitus with hepatic fibrosis by using the high-lipid-sugar diet (HLSD) combined with the inducement of CCl4 and streptozotocin. Methods SD rats were randomly divided into liver fibrosis (LF) group, type 2 diabetes combined with liver fibrosis (DLF) group, and normal group, 10 rats in each group. All rats in LF or DLE group were fed with HLSD for 4 weeks, and then all rats were intraperitoneally injected 20% carbon tetrachloride (CCl4, once in a week) according to the body weight of 5 mL/kg to induce hepatic fibrosis for another 4 weeks. During the CCl4 treatment, rats in the DLF group were also intraperitoneally injected with 25 mg/kg streptozotocin (STZ, once in a week). After STZ treatment, the content of FBG, INS, HOMA-IR, and HbA1c were evaluated once in a week. The FBG level was detected by blood glucose meter. The contents of INS and HbA1c were detected by ELISA method. Biochemical analysis was used to analyze the serum levels of AST, ALT, Tbil, and HA, as well as the HYP content in liver tissues. HE staining and Masson staining were used to evaluate the pathological changes in liver tissues. Results The contents of FBG, HbA1c and HOMA-IR in DLF group were significantly increased as compared to those in normal or LF group. While the INS content in DLF group was significantly decreased when compared to those in normal or LF group. Comparing with normal group, the high levels of ALT, AST, Tbil, HA and HYP, as well as fibrotic changes and inflammation in liver tissue were all observed in LF group and DLF group. Conclusions HLSD combined with CCl4 and streptozotocin inducement is an effective strategy to establish a rat model of type 2 diabetes mellitus with liver fibrosis.