Effect Of Emodin On Insulin Resistance And Leptin In Rat With Nonalcoholic Fatty Liver Disease Induced By High-fat Diet

Objective:we fed rats with high-fat diet for causing nonalcoholic fatty liver disease (NAFLD), then observed the function of emodin against NAFLD to probe into the influence of different dosages on insulin resistance(IR) and serum leptin, to explain the mechanisms of emodin treating NAFLD.Method:42 healthy male Spraque-Dawley rats were randomly divided into two groups:group A with 8 rats and group M with 34 rats.Group A was fed with ordinary diet and group M was fed with high-fat diet.Four weeks later, 2 rats were selected randomly from group M to get their liver tissues separately and then to dye them with HE tinction to identify if hepatic steatosis appeared. If appeared, the remaining rats in group M were indvided randomly into 4 groups with 8 in every group.Group A continue to be fed with ordinary diet and the others continue to be fed with high-fat diet.The situation was as follows:group A was fed with 0.5% sodium carboxymethyl cellulose (SCMC) by 10 mL·kg-1·d-1 for 4 weeks, group B was fed with 0.5% SCMC by 10 mL·kg-1·d-1 for 4 weeks, group C with emodin by 20 mg·kg-1·d-1 for 4 weeks, group D with emodin by 40 mg·kg-1·d-1 for 4 weeks, group E (the positive group) with metformin by 150 mg·kg-1·d-1 for 4 weeks, and all drugs in the intervention groups were dissolved by 0.5% SCMC.4 weeks later, all rats were executed.The rats'weight and their wet liver weight were got to count the liver index. The serum ALT,AST,TC,TG,LDL,HDL and glucose were measured with automatic biochemieal analyzer. Hepaticlipid (TC, TG) were also measured by enzymic methods. Liver biopsy tissues were treat by HE staining to evaluate the degree of steatosis and inflammation of liver. Oral glucose tolerance test (OGTT) was observed. The serum insulin and leptin were measured by radioimmunoassay (RIA). Insulin resistance was estimated by insulin resistance index of homeostasis model assessment (HOMA-IR) and insulin sensitivity index(ISI).Result:High-fat diet induced NAFLD model successfully in the end of the 8th week. There was no significant difference in the body weight of rats among all groups (p>0.05). The liver indexs of rats in group C and D were lower than that in group B (P<0.01). Compared with group B, the low and high dosage emodin together had the respective effect of ameliorating steatosis (p<0.05,p<0.01),and they also reduced the hepatic inflammatory activity (p<0.01). Compared with group B, the low and high dosage emodin could lower serum ALT and AST (p<0.01), and the serum ALT was lowered by emodin in a dose dependent manner (p<0.05).Compared with group B, both low and high dosage emodin reduced serum TC,TG,LDL contents and hepaticlipid(TC, TG) (p<0.01), the effect had a dose-dependent(p<0.01);and the serum HDL in group D was higher than that in group B (P<0.01). OGTT results showed, the low and high dosage emodin improved the sugar tolerance in rats, and they were significant (p<0.01). Compared with group B, the low and high dosage emodin improved insulin resistance which was represent by serum insulin,HOMA-IR and ISI (p<0.05,p<0.01).The effect of improving insulin resistance in group C was smaller than that in group E (p<0.01), and the effect of improving insulin resistance in group D was similar with that in group E (p>0.05). The serum leptin in group B was higher than that in group A (P<0.01).The serum leptin in group C and D was lower than that in group B(p<0.05, p<0.01). Correlation analysis showed that the serum leptin was positively correlated with HOMA-IR(p<0.05) and negatively correlated with ISI (p<0.05) in group B.Conclusion:1 Emodin is effective to treat NAFLD.2 Reducing serum leptin, then, raising insulin sensitivity, improving the insulin resistance may be the mechanism of emodin treating NAFLD.3 Emodin can improve lipid metabolism disorders in rats.