本文選題：肝纖維化 + 肝星狀細(xì)胞��； 參考：《大連醫(yī)科大學(xué)》2016年碩士論文

【摘要】：背景:肝纖維化(Liver Fibrosis)指肝臟內(nèi)彌漫性細(xì)胞外基質(zhì)過度沉積的病理過程,是各種慢性肝病共同的病理基礎(chǔ),目前關(guān)于肝纖維化機(jī)制的研究已經(jīng)取得了很大的進(jìn)展。肝纖維化形成的中心環(huán)節(jié)為肝星狀細(xì)胞的活化,當(dāng)肝臟受到酒精、自身免疫、肝炎病毒等因素刺激時,靜止的肝星狀細(xì)胞會轉(zhuǎn)化為具有增生性、收縮性,可表達(dá)α-平滑肌肌動蛋白(alpha Smooth Muscle Actin,α-SMA)的肌成纖維細(xì)胞,從而生成細(xì)胞外基質(zhì),最終導(dǎo)致肝纖維化的產(chǎn)生。目前關(guān)于肝星狀細(xì)胞活化的研究主要集中在細(xì)胞因子上,肝纖維化的治療也通過抑制細(xì)胞因子而發(fā)揮作用,但始終無法達(dá)到預(yù)期的療效,因此可能存在著細(xì)胞因子以外的促活化機(jī)制。目前四氯化碳誘導(dǎo)的大鼠肝纖維化模型在病理形態(tài)及特征上與人類肝纖維極其相似,因此可通過此模型探究肝星狀細(xì)胞的活化機(jī)制。目的:通過四氯化碳誘導(dǎo)的大鼠肝纖維化模型,觀察肝星狀細(xì)胞連接對肝纖維化病理過程的影響。方法:28只SD大鼠隨機(jī)分為肝纖維模型組(n=24)和對照組(n=4)。肝纖維化模型組應(yīng)用40%四氯化碳橄欖油混合溶液按照1.0ml/Kg體重對SD大鼠進(jìn)行灌胃,2次/周,持續(xù)12周建立肝纖維化模型;對照組以同一時間與肝纖維化模型組等量的蒸餾水灌胃,兩組大鼠均給予相同基礎(chǔ)飲食。利用HE染色觀察大鼠肝組織炎癥浸潤程度,Masson染色觀察大鼠肝組織纖維化程度。免疫組織化學(xué)熒光染色觀察肝星狀細(xì)胞結(jié)蛋白(Desmin)和α-平滑肌肌動蛋白(α-SMA)的表達(dá)。免疫組織化學(xué)熒光雙重染色觀察活化肝星狀細(xì)胞的形態(tài)及分布,總結(jié)肝星狀細(xì)胞活化規(guī)律,仔細(xì)觀察活化肝星狀細(xì)胞的排列方式與纖維化形成的關(guān)系。結(jié)果:1.正常肝組織(G0S0)內(nèi)無活化的肝星狀細(xì)胞,靜止肝星狀細(xì)胞均勻分布于肝竇內(nèi)。2.在肝纖維化形成前的炎癥階段(G1S0),肝竇內(nèi)的肝星狀細(xì)胞受到炎癥刺激后開始活化,此時肝星狀細(xì)胞仍均勻分布在肝竇內(nèi)。3.肝纖維化形成早期(G2S1及G3S2),肝星狀細(xì)胞活化增強(qiáng)并遷移到炎癥區(qū)域,無炎癥區(qū)域幾乎無肝星狀細(xì)胞。4.纖維間隔形成階段(S4期),肝星狀細(xì)胞較早期明顯活化,胞體增大,肝星狀細(xì)胞分布并非簡單的聚集于纖維化區(qū)域,而是呈明顯的“首尾相接”方式,展現(xiàn)了細(xì)胞“鏈接”的模式。結(jié)論:四氯化碳誘導(dǎo)SD大鼠肝纖維化模型中肝星狀細(xì)胞活化是導(dǎo)致肝纖維化的重要因素,細(xì)胞連接是纖維間隔形成的重要條件。
[Abstract]:Background: liver fibrosis refers to the pathological process of excessive deposition of diffuse extracellular matrix in the liver, which is the common pathological basis of various chronic liver diseases. At present, great progress has been made in the study of the mechanism of liver fibrosis. The central link in the formation of hepatic fibrosis is the activation of hepatic stellate cells. When the liver is stimulated by alcohol, autoimmunity, hepatitis virus and other factors, the stationary hepatic stellate cells will be transformed into proliferative and contractile cells. Myofibroblasts expressing 偽 -smooth muscle actin alpha Smooth Muscle actin (偽 -SMAA) produce extracellular matrix (ECM), leading to liver fibrosis. At present, researches on the activation of hepatic stellate cells mainly focus on cytokines. The treatment of liver fibrosis also plays a role by inhibiting cytokines, but it can not achieve the expected curative effect. Therefore, there may be a pro-activation mechanism beyond cytokines. The present rat liver fibrosis model induced by carbon tetrachloride is very similar to that of human hepatic fiber in pathological morphology and characteristics, so the activation mechanism of hepatic stellate cells can be explored by this model. Aim: to observe the effect of hepatic stellate cell junction on the pathological process of hepatic fibrosis in rats induced by carbon tetrachloride. Methods 28 Sprague-Dawley rats were randomly divided into liver fiber model group and control group. Rats in hepatic fibrosis model group were treated with 40% carbon tetrachloride olive oil mixed solution twice a week for 12 Zhou Jianli according to 1.0ml/Kg body weight, and the control group were fed with distilled water at the same time as the liver fibrosis model group, and the control group was given the same amount of distilled water at the same time as the liver fibrosis model group. Both groups were given the same basic diet. He staining was used to observe the degree of inflammatory infiltration in rat liver tissue and Masson staining was used to observe the degree of hepatic fibrosis in rats. The expression of desmin and 偽-smooth muscle actin (偽 -SMA) in hepatic stellate cells was observed by immunohistochemical fluorescence staining. The morphology and distribution of activated hepatic stellate cells were observed by immunohistochemical double staining. The relationship between the arrangement of activated hepatic stellate cells and the formation of fibrosis was carefully observed. The result is 1: 1. There were no activated hepatic stellate cells in normal liver tissue (G0S0), and stationary hepatic stellate cells distributed uniformly in sinusoidal hepatic sinuses. During the inflammatory stage before hepatic fibrosis, hepatic stellate cells in hepatic sinusoids were activated after being stimulated by inflammation, and hepatic stellate cells were still distributed in hepatic sinusoids. In the early stage of hepatic fibrosis, the activation of hepatic stellate cells was enhanced and migrated to the inflammatory region, and almost no hepatic stellate cells were found in the non-inflammatory areas. In the S4 phase of fibrous septum, hepatic stellate cells were obviously activated and their cell bodies were enlarged. The distribution of hepatic stellate cells was not simply concentrated in the fibrotic region, but in a "head-and-tail" pattern. Shows the cell "link" pattern. Conclusion: the activation of hepatic stellate cells is an important factor in hepatic fibrosis induced by carbon tetrachloride in SD rats.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R575.2

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 涂傳濤,張順財;過氧化物酶體增殖物激活受體γ與肝星狀細(xì)胞[J];肝臟;2002年02期

2 龔浩,張忠濤,王宇;血管緊張素Ⅱ與肝星狀細(xì)胞的研究進(jìn)展[J];國外醫(yī)學(xué).外科學(xué)分冊;2005年06期

3 龔浩;王宇;張忠濤;李建設(shè);馬雪梅;周延忠;;血管緊張素Ⅱ及其受體拮抗劑對肝星狀細(xì)胞Ⅰ型膠原合成的影響[J];首都醫(yī)科大學(xué)學(xué)報;2007年01期

4 張宗h，

本文編號：1806049