血红素氧合酶-1和抵抗素在非酒精性脂肪性肝病中的作用

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1、目录1血红素氧合酶-1和抵抗素在非酒精性脂肪肝的作用„„„„„„„„„„„„„„„„„„„„„„„„11.1中文摘要„„„„„„„„„„„„„„„„„„„„„11.2英文摘要„„„„„„„„„„„„„„„„„„„„„41.3前言„„„„„„„„„„„„„„„„„„„„„„„81.4材料与方法„„„„„„„„„„„„„„„„„„„„91.5结果„„„„„„„„„„„„„„„„„„„„„„„181.6讨论„„„„„„„„„„„„„„„„„„„„„„„281.7结论„„„„„„„„„„„„„„„„„„„„„„„361.8参考文献„„„„„„„„„„„„„„„„„„„„„371.9英汉缩略词对照表„„

2、„„„„„„„„„„„„„„„402致谢„„„„„„„„„„„„„„„„„„„„„„„423血红素氧合酶-1和抵抗素在非酒精性脂肪肝的作用（综述）„„„„„„„„„„„„„„„„„„„„„„„43血红素氧合酶-1和抵抗素在非酒精性脂肪性肝病中的作用摘要目的:随着生活水平的提高，饮食习惯的改变。越来越多的人患有非酒精性脂肪肝。非酒精性脂肪肝病（NASH）占平均人口的10%，在肥胖和糖尿病患者中约50%。非酒精性脂肪肝是一种常见的肝脏疾病，最终可发展包括肝硬化和肝癌。非酒精性脂肪肝(NAFLD)的表现与肝脏代谢综合征、内脏肥胖和胰岛素抵抗、氧化应激和炎症紧密联系，这些因素可能是非酒精性脂肪肝发展的

3、重要因素。本文就着重探讨血红素氧合酶-1（HO-1）和抵抗素在非酒精性脂肪性肝病（Nonalcoholicsteatohepatitis，NASH）中的作用。方法：采用雄性SD大鼠60只，体重(200g±20g).常规饲养一周后随机分为4组：对照组15只(普通饲料喂养)和非酒精性脂肪肝模型组15只，血红素氧合酶-1抑制组15只(通过高脂饮食喂养4周后与每周末进行尾静脉注射锌原卟啉抑制)和抵抗素抑制组15只（通过高脂饮食喂养4周后用西洋参夜灌胃），分别于四周末，八周末，十二周末分别处死各组老鼠5只。对大鼠的腹主动脉取血，测天门冬氨酸转氨酶(AST)、丙氨酸氨基转移酶（ALT）、血脂总胆固醇（TC

4、）、甘油三酯（TG）、肿瘤坏死因子（TNF一α）、高密度脂蛋白胆固醇(HDL—C)、低密度脂蛋白胆固醇(LDL—C)；对大鼠肝脏进行HE染色，光镜下进行肝组织病理变化的观察；对大鼠肝脏组织切片行免疫染色后，在光镜下进行血红素氧合酶-1的观察。血红素氧合酶-1的阳性细胞所占百分数和着色深浅可表明血红素氧合酶-1在大鼠肝脏组织表达的差异；用RT—PCR方法检测大鼠肝脏组织抵抗mRNA的表达。结果：非酒精性脂肪肝模型成功后观察各组变化，非酒精性脂肪肝模型组天门冬氨酸转氨酶(AST)、丙氨酸氨基转移酶（ALT）、血脂总胆固醇（TC）、甘油三酯（TG）、肿瘤坏死因子（TNF一α）、低密度脂蛋白胆固醇(L

5、DL—C)随着脂肪肝的严重程度增加。非酒精性脂肪肝模型组肝脏病理脂肪变性，坏死，炎症细胞侵润；血红素氧合酶-1抑制组肝脏病理改变较模型组更严重的脂肪变性，血红素氧合酶-1在肝脏组织的着色颜色较浅，8周末，十二周末肝脏脂肪变性较非酒精性脂肪肝模型组严重；西洋参灌胃组8周末，十二周末肝脏病理脂肪改变较非酒精性脂肪肝模型组减轻，大鼠肝脏组织抵抗素mRNA的表达较非酒精性脂肪肝模型组减少。结论：血红素氧合酶-1和抵抗素在非酒精性脂肪肝大鼠中含量都高于正常组，但其作用却不同。血红素氧合酶-1可延缓或阻止非酒精性脂肪肝的进展，血红氧合酶-1(HO-1)是降解血红素生成一氧化碳，自由铁，胆绿素的关键酶。血红

6、素的产物具有抗炎症、抗氧化、防止肝细胞坏死，抗氧化应激的作用。抵抗素来源于脂肪细胞，抵抗素会通过阻止或降低肝糖原的输入从而发生胰岛素抵抗。抵抗素在肥胖患者含量增加，与内脏脂肪性肥胖更是有密切关系，抵抗素可能是导致脂肪肝发展的因素。抵抗素通过胰岛素抵抗可加重非酒精性脂肪肝的形成，改善胰岛素抵抗可延缓非酒精性脂肪肝的发展。关键词：非酒精性肝病；血红素氧合酶-1；氧化应激；胰岛素抵抗；抵抗素TheeffectofHemeoxygenase-1andresistinonpathogenesisofnonalcoholicfattyliverdiseaseabstractObjective:withth

7、eimprovementoflivingstandards,andthechangeofeatinghabits,moreandmorepeoplearesufferfromnonalcoholicfattyliverdisease.Nonalcoholicsteatohepatitis(NASH)accountsforanaverage10%ofthepopulation,especiallyi