微血栓在非酒精性脂肪性肝炎肝纤维化发病中作用.pdf

复曼大学弼±辑变生论文 微斑拴在非游撞致￡匕翳性翳炎翳纤维纯发病中的璺用 【结论1持续24周的商脂饮食可成功复制非酒精性脂肪性肝炎并肝纤维化动物模 型，该模型大鼠普遍存在肝窦内皮功能障碍和凝血纤滚状态改变，并有2 只造模大鼠肝寞内发现微m栓，而抗血栓类药物有减轻肝内炎症及纤维化 的作用，提示微血栓及其相关因子参与NASH纤维化的发病。 I关键词l非酒精性脂肪性肝炎肝纤维化徽血栓抗觑栓炭药物 分类号：R575．5 2 复旦大学硕士研究生论文 微血栓在非酒精性脂肪性肝炎肝纤维化发病中的作用 ABSTRACT The role ofthe microthrombin in the development ofnon-alcoholic steatohepatitis and fibrosis 【Objeetives]To study the effects of the microthrombin on the development of non—alcoholic steatohepatitis and fibrosis by detecting the factors which take part in the microthrombus and interfering the animal model with anti—thrombic drugs． [Methods]SD rats were fed with high-fat diet consisted of normal diet．10％lard oil and 2％cholester01．After 5 weeks high-fat diet，some rats are interfered with dan-shen root，pentoxifylline and clopidogrel．All rats sacrified at the 8th,12th,16th and 24th week respectively．Body weight，liver weight，serum level of liDid and aminotransferase were measured．The degrees of hepatosteatosis，inflammation,and fibrosis of liver were investigated by HE stain and VG stain．The factors concerning microthrombus detected either in blood or in liver tissues included white blood cells(wBc)，C—reactive protein (CRP),thromboxane B2(TXB2)， 6-keto—prostaglandin F1 a (6一keto·PGFl。),endothelin-1(ET·1)，nitric oxide(NO)，tissue plasminogen activator(tPA)，plasminogen activator inhibkor-l(PAI一1)and platelet-derived growth factor(PDGF)． 【Results]The rats fed high-fat diet developed fatty liver at the 8th week，steatosis from thel2th weel to the 24th week．Hepatic fibrosis Was observed at the 16th week and the 24th week．To compare with normal group，in model group，WBC and CRP are no changes．and the serum level of NO i11 blood increased．From the 8th week to the 24th week,the plasma level of tPA and 6．keto．PGFl。 decreased，while the level of TXB2 and TXB2／6-keto．PGFl。increased．The hepatic expressions of ET and PAI一1 were up-regulated in model group by immunohistochemlstry．The hepatic expression of ET-lmRNA，PAI．1mRNA and PDGFmRNA we