| Ojective: With the accelerating pace of modern life,and people indulging in unhealthy diets and bad living habits, nonalcoholic fatty liver disease(NAFLD) has become a important cause of chronic liver disease. Presertly,the pathogenesis of NAFLD is complex,it is not fully clear.Studies show that many factors involved in the pathogenesis of NAFLD, including insulin resistance,abnormal lipid metabolism,oxidative stress and increased apoptosis susceptibility,etc. But those factors still cannot fully explain the pathogenesis of NAFLD.Can we study on the basis of effectively established animal model of NAFLD? Visfatin playing a key role in the pathogenesis of NAFLD is controversial.Studies found that Visfatin could induce fatty degeneration of liver cells,and promote the occurrence of NAFLD. ZAG plays a protective role in the pathogenesis of NAFLD by means of regulating lipid metabolism in the body. Can we study Visfatin and ZAG on the basis of the animal model of NAFLD? Turmeric is a common traditional Chinese medicine,which is able to promote flow of qi and blood circulation and induce menstruation to relieve menalgia. Recent studies suggest its is of antioxidant, removing of oxygen free radicals,anti-inflammatory effect.Curcumin is the active ingredient of turmeric.Researches show that it has a certain therapeutic effect on NAFLD,but the specific mechanism is still not clear.Can we study the effects of curcumin on NAFLD animal model?Whether is it effective in the treatment of NAFLD?What is the mechanism of curcumin on protective process in NAFLD?Whether is the efficacy of Curcumin through regulating the expression of of Visfatin and ZAG?The study finds that curcumin has a low biological utilization rate. Multiple studies use different doses of curcumin to find the effect of NAFLD,but there is no different doses of contrast experiment.Studies have confirmed that different doses of curcumin have different effects on ulcerative colitis.Can we prove the effects of different doses of curcumin on NAFLD?Methods : Select 56 male SD rats,adaptive feeding for one week.Rats were divided to normal group(16 rats) and model group(40 rats)randomly.The rats of normal group were fed with normal diet,and the rats of model group were fed with high fat diet.Each rat was free acess to water.8 rats were excuted from normal group and model group at the end of 8 weeks, the liver pathology examination was done.After confirming to successfully made a nonalcoholic liver disease animal model,the rats of model group were divided into four groups(low dose group, middle dose group, high dose group, control group).There were 8 rats in each group,and high fat diet was fed continuously.The rats of low dose group were given intragastric administration of 50mg/kg curcumin daily.The rats of middle dose group were given intragastric administration of 100mg/kg curcumin daily.The rats of high dose group were given intragastric administration of 200mg/kg curcumin daily.The rats of control group were given equal volume of CMC for 4 weeks.The rats of normal group were fed with normal diet,and given equal volume of CMC for 4- 6-weeks. All animals after fasting for 12 h were executed at the end of the 12 week,heart blood was drawn to test ALT,AST,TG,TC,FBG and FINS,then calculated the HOMA-IR.The liver tissue of rats was quickly cut, weighed.One part of the liver tissue were made to take pathological examination and immunohistochemical determination expression of Visfatin, and ZAG.The other part of the liver tissue was used to detect visfatin m RNA expression after frozen and storage-80℃ with lidud nitrogen.Results:1.Compared with the normal group,the liver index, serum ALT, AST, TG, TC, FINS, FBG and HOMA-IR in modle group were increased.And the difference was statistically significant between the two groups(P<0.01).2.Along with the prolonging time of high fat feeding, the liver index, serum ALT, AST, TG, TC, FINS, FBG and HOMA-IR in the two stage of model group were increased(P<0.05).3.Compared with the same period model group,the liver index, serum ALT, AST, TG, TC, FINS, FBG and HOMA-IR of low, middle and high dose groups decreased(P<0.05), but higher than those of the control group(P<0.05).There was significant difference between those of low,middle and high dose group(P<0.05),except the liver index, TG,FINS, FBG.4.Compared with the normal group,the Visfatin expression in liver tissue of modle group increased(P<0.01),and the ZAG expression in liver tissue of modle group decreased(P<0.01).5. Along with the prolonging time of high fat feeding, the two phase of liver tissue Visfatin expression in model group were increased(P<0.01), the expression of ZAG was decreased(P<0.01). 6.Compared with the model group,Visfatin expression in the liver tissue of low,middle and high dose group decreased(P<0.01), the expression of ZAG increased(P<0.05), but did not return to normal(P< 0.05).And there was significantly difference between the low,middle and high dose group(P<0.05).Conclusion:1.NAFLD rats model can be successfully established through high-fat diet fed after a certain period of time,in which rats had hyperlipidemia,hyperinsulinemia and liver steatosis, steatohepatitis changes. 2.Visfatin can induce fatty degeneration of liver cells,and promote the occurrence of NAFLD. ZAG plays a protective role in the pathogenesis of NAFLD by means of regulating lipid metabolism in the body. 3.HOMA-IR, TG, TC levels decreased,along with the serum levels of ALT, AST decreased significantly and liver histopathologicalimprovement,after curcumin treated NAFLD rats.4.The efficacy of curcumin maybe through regulating level of Visfatin and ZAG(decreased Visfatin level and increased ZAG level).5 Different concentrations of curcumin have different effects on the treatment of NAFLD rats. In high dose group(200mg/kg/d) treatment effect was best. |