摘要
目的观察褪黑素(melatonin,MT)对非酒精性脂肪性肝炎大鼠肝脏CYP2E1表达的影响。方法雄性Wistar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周,各MT干预组依次给予MT(含≤1%无水乙醇)2.5mg·kg-1.d-1、5.0mg·kg-1.d-1、10mg·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周末进行肝脏病理学检查。生化法测定肝匀浆三酰甘油(TG)、总胆固醇(TC)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱苷肽过氧化物酶(GSH-Px)值,免疫组化法检测肝脏CYP2E1的表达。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,肝匀浆TG、TC、MDA值明显升高(P<0.01);肝匀浆SOD、GSH-Px明显降低,CYP2F1表达强度增加。与模型组比较,各MT干预组肝脏病理变化逐渐改善,肝匀浆TC、TG、MDA值逐渐降低,肝匀浆SOD、GSH-Px活力则逐渐升高,MT高剂量组肝脏CYP2E1表达减弱(P<0.05)。结论MT能显著抑制非酒精性脂肪性肝炎大鼠肝脏CYP2E1的表达,提高抗氧化酶活性,抑制脂质过氧化反应。
Objective To observe the effects of melatonin on hepatocyte cytochrome P450 2E1 （CYP2E1） expression in rats with nonalcoholic steatohepatitis. Methods Fifty male Wistar rats were randomly divided into 5 groups with 10 for each. The melatonin in low does, moderate does, high does group and model group were fed with high fat diet while the normal control group with common diet for 12 weeks. Melatonin （contains≤1% dehydrated alchol） was intraperitoneally injected to the rats in various melatonin groups （2.5 mg/kg, 5 mg/kg, and 10 mg/kg, respectively） and equal does of saline （contain 1% dehydrated alcohol） to normal control group and model group once a day. Histopathologieal changes in liver were observed. The levels of liver tissue homogenates triglyceride （TG）, total cholesterol （TC）, superoxide dis- mutase （SOD）, malondialdehyde （MDA） and GSH-peroxidase （GSH-Px） were measured by biochemical methods. The expression of CYP2E1 in liver was observed by immunohistochemical method. Results Compared with normal control group, the model group developed middle-serious steatosis, the levels of liver tissue homogenates TC, TG, MDA increased （P 〈0.01 ） and the expression of CYP2E1 in liver enhanced, liver tissue homogenates SOD and GSH-Px decreased （P 〈 0.05）. Compared with model group, the levels of TC, TG, MDA in liver tissue homogenates decreased, GSH-Px, SOD increased, pathological changes in liver was improver in melatonin-treated groups. The expression of CYP2E1 in liver of rats treated with high does of MT was inhibited （P 〈 0.05）. Conclusion Melatonin can inhibit the hepatocyte CYP2E1 expression, improve antioxidase activity and depress lipid peroxidation in rats with noncoholic steatohepatitis.
出处
《胃肠病学和肝病学杂志》
CAS
2009年第7期604-607,共4页
Chinese Journal of Gastroenterology and Hepatology
基金
安徽省教育厅科研基金资助项目(2002KJ139)
关键词
非酒精性脂肪性肝炎
CYP2E1
脂质过氧化
褪黑素
Nonalcoholic steatohepatitis
Hepatoeyte cytochrome P450 2E1
Lipid peroxidation
Melatonin
