本文選題：細(xì)胞自噬　切入點(diǎn)：肝纖維化　出處：《廣東醫(yī)學(xué)》2017年15期

【摘要】：目的探討細(xì)胞自噬影響實(shí)驗(yàn)性大鼠肝纖維化進(jìn)展的分子機(jī)制以及藥物抗肝纖維化的作用。方法將49只SD老鼠隨機(jī)分成正常對(duì)照組、模型對(duì)照組、藥物治療組[熊去氧膽酸(UDCA)組、雷帕霉素(RAPA)治療組、羥氯喹(HCQ)治療組、羥氯喹和熊去氧膽酸(HCQ+UDCA)治療組、雷帕霉素和羥氯喹(RAPA+HCQ)治療組]。造模后分給予媒介、自噬促進(jìn)劑雷帕霉素(RAPA)、自噬抑制劑羥氯喹(HCQ)、熊去氧膽酸(UDCA)單用或者合用灌胃。治療4周后,處死所有的老鼠收集肝標(biāo)本。HE染色檢測(cè)肝病理變化。Western blot技術(shù)檢測(cè)自噬相關(guān)分子ATG-5、Beclin-1以及LC-3Ⅱ。同時(shí),血液標(biāo)本生物化學(xué)方法檢測(cè)肝功能以及單胺氧化酶(MAO)。結(jié)果與模型對(duì)照組相比,RAPA治療組大鼠肝重、肝指數(shù)、膠原指數(shù)、肝纖維化評(píng)分均顯著性升高(P0.05),而其他治療組大鼠顯著降低(P0.05)。但病理顯示HCQ或者與其他藥物合用不能改善肝組織細(xì)胞壞死和脂肪樣變性。Western blot顯示與正常對(duì)照組肝組織相比,模型對(duì)照組肝組織中ATG-5、Beclin-1、LC3-Ⅱ表達(dá)量顯著增加(P0.05);與模型對(duì)照組鼠肝組織相比,UDCA治療組和HCQ+UDCA治療組肝組織自噬相關(guān)蛋白表達(dá)顯著性降低(P0.05),其他治療組與模型對(duì)照組相比ATG-5、Beclin-1、LC3-Ⅱ表達(dá)量明顯增強(qiáng)。此外,所有的治療組大鼠血清TBIL、AST、ALT比模型對(duì)照組顯著性降低(P0.05);而與模型對(duì)照組相比,RAPA治療組MAO明顯增加(P0.05),其他治療組則明顯降低(P0.05)。結(jié)論肝纖維化可能涉及到肝臟中細(xì)胞自噬水平變化,調(diào)節(jié)細(xì)胞自噬既影響肝臟肝纖維化同時(shí)也影響肝臟組織細(xì)胞變性以及肝功能。UDCA改善肝臟肝纖維化可能與其調(diào)節(jié)細(xì)胞自噬有關(guān),調(diào)節(jié)細(xì)胞自噬可能為治療肝纖維化一個(gè)新的切入點(diǎn)。
[Abstract]:Objective to investigate the molecular mechanism of autophagy on the progression of experimental hepatic fibrosis in rats and the effect of drugs on hepatic fibrosis.Methods Forty-nine Sprague-Dawley rats were randomly divided into normal control group, model control group, ursodeoxycholic acid UDCA-treated group, rapamycin RAPA treatment group, hydroxychloroquine HCQ-treated group, hydroxychloroquine and ursodeoxycholate HCQ UDCA-treated group.Rapamycin and hydroxychloroquine RAPA HCQ treatment group].After modeling, they were divided into two groups: autophagy accelerator rapamycin (Rapa), autophagy inhibitor hydroxychloroquine (HCQ), ursodeoxycholic acid (UDCA), and single or combined administration of ursodeoxycholic acid (UDCA).After 4 weeks of treatment, all the mice were killed to collect liver samples. The pathological changes of liver were detected by HE staining. Western blot technique was used to detect autophagy related molecules ATG-5, Beclin-1 and LC-3 鈪，

本文編號(hào)：1689230