本文選題：肝纖維化　切入點：硫化氫　出處：《蘇州大學》2014年碩士論文

【摘要】：目的： 探討內(nèi)源性H2S對實驗性肝纖維化大鼠AT1表達的影響，來推測內(nèi)源性H2S在大鼠肝纖維化發(fā)病中的作用機制。 方法： 健康Wistar雄性大鼠56只，隨機分為4組：正常對照組、模型組、PAG組、NaHS組，對除正常對照組以外各組大鼠建立以CCl4誘導(dǎo)的大鼠實驗性肝纖維化模型，并對PAG組腹腔注射胱硫醚-γ-裂解酶(CSE)抑制劑DL-炔丙基甘氨酸（PAG），NaHS組腹腔注射H2S供體硫氫化鈉（NaHS），正常對照組及模型組注射等量的生理鹽水。各組大鼠于造模后3周、4周后處死，各組大鼠于3、4周分別，用放射免疫法檢測大鼠肝纖維化指標：血清透明質(zhì)酸酶（HA），層粘蛋白（LN），III型前膠原（PcIII），IV型膠原（cIV），全自動生化檢測儀檢測肝功能變化：血ALT，AST，白蛋白（ALB值），病變肝臟的組織學變化（HE和Masson染色病理切片），采用免疫印記法檢測血管緊張素II受體1(AT1)的表達水平，以實時熒光定量RT-PCR測定胱硫醚-γ-裂解酶(CSE)的mRNA含量變化，采用去蛋白的方法測定血清中H2S含量。 結(jié)果： 1）同一時間點組織學損傷評分在模型組、PAG組、NaHS組均顯著高于正常對照組，PAG組明顯高于模型組，NaHS組則明顯低于模型組和PAG組（P＜0.05）。 2）血清透明質(zhì)酸酶（HA），層粘蛋白（LN），III型前膠原（PcIII），IV型膠原（cIV），血ALT，AST水平在模型組、PAG組、NaHS組均顯著高于正常對照組，PAG組明顯高于模型組，NaHS組則低于模型組，白蛋白（ALB值）的變化趨勢相反（P＜0.05）。 3）肝臟CSEmRNA表達水平在模型組、PAG組、NaHS組均顯著高于正常對照組，PAG組明顯高于模型組，，NaHS組則低于模型組（P＜0.05）。 4）肝臟AT1表達水平在模型組、PAG組、NaHS組均高于正常對照組，PAG組明顯高于模型組，NaHS組則低于模型組（P＜0.05）。 5）血漿H2S含量在模型組、NaHS組均明顯高于正常對照組，PAG組低于模型組，而NaHS組明顯高于PAG組和模型組（P＜0.05）。 結(jié)論： 內(nèi)源性H2S與大鼠四氯化碳實驗性肝纖維化有明顯相關(guān)性，在一定范圍內(nèi)有抗纖維化的作用，且降低了大鼠肝臟AT1的表達，推測可能通過降低AT1的表達的機制來抑制肝纖維化的發(fā)生和發(fā)展。
[Abstract]:Objective:To explore the effect of endogenous H2S on the expression of AT1 in rats with experimental hepatic fibrosis, and to speculate the mechanism of endogenous H2S in the pathogenesis of hepatic fibrosis in rats.Methods:56 healthy male Wistar rats were randomly divided into 4 groups: normal control group, model group and nahs group. Experimental hepatic fibrosis model induced by CCl4 was established in each group of rats except the normal control group.The PAG group was treated by intraperitoneal injection of cystathionine-gamma lyase (DL-propargylglycine) inhibitor DL-propargyl glycine (PAGG) NaHS group and the normal control group and the model group were injected with the same amount of normal saline.The rats in each group were killed at 3 weeks and 4 weeks after the establishment of the model, and the rats in each group were killed at 3 weeks and 4 weeks, respectively.The indexes of hepatic fibrosis in rats were detected by radioimmunoassay: serum hyaluronidase, laminin (laminin), procollagen type III, procollagen type IV, and liver function were detected by automatic biochemical instrument: serum ALTAST, Albumin's ALB value, pathological liver tissue.The expression of angiotensin II receptor 1 (AT1) was detected by immunological imprinting method.The changes of mRNA content in cystathionine-gamma lyase (CSE) were determined by real-time fluorescence quantitative RT-PCR, and the serum H2S content was determined by deproteinization method.Results:1) at the same time, the histological injury scores in the model group were significantly higher than those in the normal control group (P < 0.05), and were significantly higher than those in the model group and the PAG group (P < 0.05).3) the expression of CSEmRNA in the model group was significantly higher than that in the normal control group (P < 0.05).4) the expression of AT1 in the model group was significantly higher than that in the normal control group (P < 0.05).5) the plasma H2S content in the model group was significantly higher than that in the normal control group (P < 0.05), while that in the NaHS group was significantly higher than that in the PAG group and the model group (P < 0.05).Conclusion:Endogenous H2S has a significant correlation with experimental hepatic fibrosis of carbon tetrachloride in rats, and has anti-fibrosis effect to a certain extent, and decreases the expression of AT1 in rat liver.It is speculated that the pathogenesis and development of hepatic fibrosis may be inhibited by decreasing the expression of AT1.
【學位授予單位】：蘇州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R575.2

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