發(fā)布時(shí)間：2018-03-31 09:25

  本文選題：酒精　切入點(diǎn)：HBV轉(zhuǎn)基因小鼠　出處：《中南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)》2017年03期

【摘要】：目的:觀察在肝損傷早期,拉米夫定和水飛薊素對(duì)酒精刺激的乙型肝炎病毒(hepatitis B virus,HBV)轉(zhuǎn)基因小鼠肝組織保護(hù)作用,并通過(guò)檢測(cè)肝纖維化相關(guān)因子探討其機(jī)制。方法:將40只1.3拷貝HBV轉(zhuǎn)基因BALB/C小鼠隨機(jī)分為4組。對(duì)照組以生理鹽水灌胃;模型組以體積分?jǐn)?shù)為50%的白酒5 m L/kg灌胃,1次/d;拉米夫定組在模型組處理基礎(chǔ)上以拉米夫定溶液(100 mg/kg)灌胃,1次/d;水飛薊素組在模型組處理基礎(chǔ)上以水飛薊素溶液(200 mg/kg)灌胃,1次/d。10周后熒光定量PCR檢測(cè)各組小鼠血清HBV-DNA載量,全自動(dòng)生化儀檢測(cè)血清ALT和AST水平。HE染色,Masson染色鏡檢觀察肝組織病理變化,熒光實(shí)時(shí)定量PCR檢測(cè)肝組織TGF-β1,Smad3,Smad7,結(jié)締組織生長(zhǎng)因子(connective tissue growth factor,CTGF)mRNA表達(dá)水平,免疫組織化學(xué)檢測(cè)肝組織TGF-β1,CTGF,α-平滑肌肌動(dòng)蛋白(α-SMA)表達(dá)水平。結(jié)果:與對(duì)照組相比,模型組肝組織病理?yè)p傷加重,血清HBV病毒載量,ALT和AST水平明顯增高,肝組織內(nèi)TGF-β1,Smad3,Smad7,CTGF mRNA及TGF-β1,CTGF,α-SMA蛋白表達(dá)增加(P0.05)。與模型組相比,拉米夫定組和水飛薊素組肝組織病理?yè)p傷均減輕,肝組織內(nèi)TGF-β1,Smad3,CTGF mRNA及TGF-β1,CTGF,α-SMA蛋白表達(dá)減少(P0.05),Smad7 mRNA的表達(dá)進(jìn)一步增加(P0.05),水飛薊素組血清ALT和AST水平降低(P0.05)。結(jié)論:拉米夫定和水飛薊素可通過(guò)調(diào)節(jié)TGF-β1/Smads信號(hào)通路,減少CTGF表達(dá),抑制肝星狀細(xì)胞活化等機(jī)制阻斷酒精刺激的HBV轉(zhuǎn)基因小鼠肝組織纖維化的發(fā)生和進(jìn)展。
[Abstract]:Aim: to observe the protective effect of lamivudine and silymarin on liver tissue of alcoholic hepatitis B virus hepatitis B virus (HBV) transgenic mice at the early stage of liver injury, and to explore the mechanism of liver fibrosis related factors.Methods: forty 1.3 copy HBV transgenic BALB/C mice were randomly divided into 4 groups.In the control group, normal saline was administered to the stomach.The model group was fed with 5 m L/kg of 50% volume fraction, the lamivudine group was given 100 mg / kg lamivudine solution on the basis of the model group, and the silymarin group was treated with silymarin solution on the basis of the model group.The serum HBV-DNA load of each group was measured by fluorescence quantitative PCR 10 weeks after intragastric administration of 200 mg 路kg ~ (-1) 路d ~ (-1).The levels of serum ALT and AST were detected by automatic biochemical instrument. The pathological changes of liver tissue were observed by HE staining and Masson staining. The expression of TGF- 尾 1, Smad3 Smad7, connective tissue growth factor- 鈪，

本文編號(hào)：1690126