| ObjectiveTo establish the model of nonalcoholic fatty liver disease and investigate the expression of level of serum transaminase,glucose,lipid SOD,MDA,GSH-PX, hepatic morphology and hepatic PKB,P-PKB,P-PKB/PKB,effects of N-acetylcysteine and melatonin.on above-mentioned indexs.Methods1.(the part of N-acetylcysteine) eighty male male Wistar rats were randomly divided into 5 groups with 16 rats in each group.The rats in the normal control group were fed with normal diet while that in the model group,the N-acetylcysteine in low dose group,moderate dose,high dose group with high-fat diet.The rats in various groups were treated with N-acetylcysteine 10 mg /(kg·d),20mg /(kg·d),40mg / (kg·d)and equal doses of saline to control and model group once a day by intragastric administration respectively.After 10 weeks feeding,before to put to death, half mice from each group were either injected insulin(2.5 U) or similar volume of NS in the portal vein,5 min before the resection of the liver,liver humid weight and liver index and Histopathological changes in liver were observed.The level of alanine aminotransferase(ALT)and aspartate aminotransferase(AST) in serum,the level of total cholesterol(TC)and triglyceride(TG) in liver tissue homogenates were measured by biochemical method.The expression of PKB,P-PKB and the ratio of P-PKB/PKB in hepatocytes were tested by immunohistochemistry.2.(The part of melatonin)The dividing of group,the administration and the materials of drawing from animals were from the research of the early days.The concret method is as follows:50 male Wistar rats were randomly divided into 5 groups with 10 rats in each group.The rats in the normal control group were fed with normal diet while that in the model group,the melantonin in low dose group,moderate dose,high dose group with high-fat diet.The rats in various melatonin groups were treated with melatonin 2.5 mg /(kg·d),5.0mg /(kg·d),10.0 mg /(kg·d)by intraperitoneal injection respectively.After 12 weeks feeding,the other indexs were detected as the part of acetylcysteine.Results1.(the part of acetylcysteine) the NAFL/NASH rat model was successfully established with high fat diet for 10 weeks.compared with control group,liver humid weigh,liver index increased in model group and developed steatosis and focus infiltration of inflammatory cells and punctiform necrosis in hepatic lobules.The level of serum ALT,AST,TC,GLUand TC,TG;MDA in liver tissue homogenates increased significantly(P＜0.05).simultaneously with decrease on liver SOD,GSH-PX(P＜0.05). The expression of hepatic PKB,P-PKB and the ratio of the two in the model group with or without injecting insulin were lower than the control group (P＜0.05).The expression of hepatic PKB,P-PKB and the ratio of the two in the control group with injecting insulin were higher than the same group without injecting insulin(P＜0.05).The expression of hepatic PKB,P-PKB and the ratio of the two in the model group with injecting insulin were higher than the same group without injecting insulin,But the diffence between two has no significant meaning(P＞0.05).Compared with model group,N-acetylcysteine in dose of moderate and high group improved the pathological changes in liver with steaosis and the decrease of histological activity index(P＜0.05),the level of liver humid weigh,MDA SOD,GSH- PX in liver tissue homogenates(P＜0.05).N-acetylcyeteine in dose of high group improved the level of liver index,serum AST,GLU;TC,TG in liver tissue homogenates.The expressions of hepatic PKB,P-PKB and the ratio of the two in the moderate and high dose of NAC were higher than the model group with or without injecting insulin(P＜0.05).The expressions of hepatic PKB,P-PKB and the ratio of the two in the moderate and high dose of NAC with injecting insulin are higher than the same group without injecting insulin(P＜0.05).2.(The part of melatonin) Compared with control group,the model group developed steatosis and foucus infiltraion of inflammatory cells and punctiform necrosis in hepatic lobules,with significant increase on liver humid weight,liver index,serum ALT,GLU(0.05),AST,TC(P＜0.01),andTC,TG,MDA in liver tissue homogenate(P＜0.05),simultaneously with decrease on liver SOD,GSH-PX(P＜0.05).The expression of PKB,P-PKB,the ratio of P-PKB and PKB in liver was increased.Compared with model group,melatonin improved the pathological changes in liver with steaosis and the decrease of histological activity index(P＜0.05),the level of MDA in liver tissue homogenate,liver index,liver humid weight(P＜0.05, P＜0.01),simultaneously with the increased of SOD,GSH-Px in liver tissue homogenate(P＜0.05)in moderate and high dose of MT group.The level of serum AST, liver tissue homogenate TC,TG in high dose of MT group and the level of liver tissue homogenate TC in moderate dose of MT group was lower than model group (P＜0.05).The expressions of PKB,P-PKB in moderate and high dose of MT group and the ratio of the two were improved in high dose of MT group.Conclusions The expression of hepatic PKB,P-PKB,P-PKB/PKB decreased in rats with NAFL/NASH.N-acetylcysteine and Melatonin can improve lipid both in serum and liver tissue homogenates,hepatic morphology.Its protective mechanism may be correlated with anti-oxidative stress and up-regulating the expression of hepatic PKB or(and) improving hepatic insulin sensitivity.
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