褪黑素对高脂饮食大鼠非酒精性脂肪性肝炎中氧化抗氧化系统的影响

Effects of melatonin on oxidation,antioxidation in nonalcoholic steatohepatitis rats fed with high fat diet

目的：观察褪黑素(MT)对非酒精性脂肪性肝炎大鼠肝脏形态学及肝内脂质和氧化抗氧化系统的影响。方法：雄性Wister大鼠50只,随机分成5组每组10只,正常对照组予普通饲料,模型组、MT低剂量组、MT中剂量组、MT高剂量组予高脂饮食12 wk。各MT干预组依次给予MT(含≤1%无水乙醇)2.5 mg·kg^(-1)·d^(-1),5.0 mg·kg^(-1)·d^(-1)和10.0 mg·kg^(-1)·d^(-1)腹腔注射,正常对照组、模型组予等量生理盐水(含1%无水乙醇)腹腔注射,12 wk末进行肝脏病理检查,生化法测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肝匀浆三酰甘油(TG)、总胆固醇(TC)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)值。结果：与正常对照组比较,模型组大鼠肝细胞呈中-重度脂肪变性,血清ALT,AST,肝匀浆TG,TC,MDA值明显升高(P＜0.05),SOD,GSH-PX值明显减低(P＜0.05)；与模型组比较,各MT干预组肝脏病理变化改善,ALT,AST,TC下降,随MT剂量增高MDA值逐渐降低(P＜0.01),SOD,GSH-PX值则升高(P＜0.01,0.02＜P＜0.05)。结论：MT能明显改善高脂饮食大鼠脂肪肝形态学变化,提高抗氧化酶活性,抑制脂质过氧化反应,因而对非酒精性脂肪性肝炎有防治作用。

AIM： To investigate the effects of melatonin on hepatic morphology,lipid and the system of oxidation and antioxidation in nonalcoholic steatohepatitis rats. METHODS： Fifty male Wistar rats were divided into 5 groups with 10 for each randomly. The melatonin in low dose,moderate dose,high dose group and model group were fed with high fat diet while the control group with common diet for 12 wk. Mehatonin （contain ≤ 1% dehydrated alcohol） was intraperitoneally injected to the rats in various melatonin groups （2.5 mg·kg^-1·d^-1, 5.0 mg·kg^-1·d^-1,and 10.0 mg·kg^-1·d^-1 respectively） and equal dose of saline （contain 1% dehydrated alcohol） to control and model groups once a day. Histopathological changes aminotransferase CAST）, alanine aminotransferase （ALT） in liver were observed. The level of serum aspartate , liver tissues homogenates triglyceride （TG）, total cholesterol （TC）, superoxide dismutase （SOD）, malondialdehyde （MDA） and GSH-peroxidase （GSH-PX）were measured by biochemical methods. RESULTS： Comparing with control group ,the model group developed middle-heavy steatosis with significant increase on level of serum ALT, AST, liver tissue homogenates TC and MDA （P 〈 0.05）, simultaneously with decrease on tissue homogenates SOD and GSH-PX （P 〈 0.05）. Comparing with model group, the level of serum ALT,AST, liver tissue homogenates TC decreased and pathological changes in liver was improved in melatonin-treated groups;the decrease of MDA （P 〈 0.01）and the increase of GSH-PX, SOD （P 〈 0.01,0.02 〈 P 〈 0.05） was correlated with the increase of melatonin dose. CONCLUSION： Melatonin can significantly improve morphology,antioxidase activity and depress lipid peroxidation of fatty liver, presenting the protective and therapeutic effects for nonalcoholic steatohepatitis.