Protective effect and mechanism of Hirudo on mice with non-alcoholic fatty liver disease
OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease(NAFLD)in mice.METHODS The male ApoE-/-mice were randomly divided into the model group and Hirudo low-dose and high-dose groups(0.45,0.9 g/kg),with 10 mice in each group;another 10 wild-type male C57BL/6J mice were chosen as the control group.The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model.Each administration group was given corresponding solution intragastrically,once a day,for 8 consecutive weeks.In the 13th week,the body weight and liver weight of mice in each group were measured after the last medication,and the liver index was calculated;the serum levels of nuclear factor-κB(NF-κB),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected;the liver pathomorphological changes were observed;the protein expressions of peroxisome proliferator-activated receptor γ(PPARγ)and silence information regulator type 1(SIRT1)were detected.RESULTS Compared with the control group,the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells,with significant lipid accumulation;the body weight,liver weight and liver index of the mice,and serum levels of NF-κB,TNF-α,IL-1β,IL-6,TC,TG and LDL-C significantly increased,while the serum level of HDL-C,the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased(P<0.01).Compared with the model group,the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups;the body weight,liver weight and liver index,the serum levels of NF-κB,TNF-α,IL-1β,IL-6,TC,TG and LDL-C decreased significantly,while the serum level of HDL-C,the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly(P<0.05 or P<0.01).CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1,thus having a significant ameliorative effect on NAFLD.