摘要目的 观察大黄素对非酒精性脂肪肝大鼠胰岛素抵抗、瘦素的作用,探讨其防治脂肪肝的可能机制.方法 将42只SD大鼠按体重大小编号后采用随机数字表法分为2组:正常组(A组、8只),给予普通饲料喂养；高脂饲料喂养组(M组、34只),给予高脂饲料喂养.于4周末验证有脂肪肝后,M组32只大鼠按体重大小编号后用随机数字表法分为M1、M2、M3、M4四个亚组,每组8只,各大鼠饲养饲料不变,其中,M2、M3、M4组分别予低剂量大黄素、高剂量大黄素、二甲双胍干预,大黄素、二甲双胍以0.5％羧甲基纤维素钠溶解,A组、M1组予0.5％羧甲基纤维素钠灌胃.8周末测定血清瘦素、稳态模式评估法胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI),评价肝脂肪变和炎症程度.结果 与M1组比较,低、高剂量大黄素均能改善由HOMA-IR和ISI所评价的胰岛素抵抗(P ＜0.05,P＜0.01).M1组血清瘦素较A组升高(P＜0.01),M2、M3组血清瘦素较M1组降低(P ＜0.05,P＜0.01)；M1组血清瘦素水平与HOMA-IR呈正相关(r=0.746,P＜0.05),与ISI呈负相关(r=-0.731,P＜0.05).与M1组比较,低、高剂量大黄素对大鼠肝脏脂肪变有不同改善(P ＜0.05,P＜0,01),而对肝脏炎症均有改善(P＜0.01).结论 大黄素降低血清瘦素水平,改善胰岛素抵抗,可能是其防治大鼠非酒精性脂肪肝的重要机制之一.

abstractsObjective To investigate the effect of emodin on insulin resistance and leptin in rat with nonalcoholic fatty liver disease (NAFLD) and to explore the mechanisms of emodin treating NAFLD.Methods Forty two Spraque-Dawley rats were numbered according to their body weights,and were randomly divided into two groups(group A:8 rats; group M:34 rats) by random number table method.The rats in group A was fed with ordinary diets and Group M with improved high fat diets.Four weeks later,when hepatic steatosis in group M were identified,the remaining 32 rats in group M were numbered according to their body weights,and were divided randomly into 4 subgroups (group M1,M2,M3 and M4) by random number table method,with 8 rats in each subgroup.The feeding of all rats was unchanged.The rats in group M2,M3 and M4 were separately intervened with emodin by low doses,emodin by high doses and metformin.Emodin and metformin were dissolved by 0.5％ sodium carboxymethyl cellulose.The rats in group A and M1 was fed with 0.5％ sodium carboxymethyl cellulose by gavage.Four weeks later,all rats were executed.The serum glucose was measured with automatic biochemical analyzer.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).Liver biopsy tissues were treated by Hematoxylin-eosin (HE) staining to evaluate the degree of steatosis and inflammation of liver.Results Compared with group M1,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 serum leptin in group M1 was higher than that in group A (P ＜0.01).The serum leptin in groups M2 and M3 was lower than that in group M1(P ＜0.05,P ＜0.01).Correlation analysis showed that the serum leptin was positively correlated with HOMA-IR(r =0.746,P ＜0.05),and negatively correlated with ISI(r =-0.731,P ＜ 0.05)in group M1.Compared with group M1,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).Conclusions Reducing serum leptin and improving insulin resistance may be the mechanisms of emodin treating NAFLD.