【摘要】：目的探討肌醇需求激酶1(IRE1)介導(dǎo)的內(nèi)質(zhì)網(wǎng)應(yīng)激(ERS)細(xì)胞凋亡途徑在多聚鳥苷酸(PolyG)干預(yù)大鼠矽肺纖維化中的作用及機(jī)制。方法將無(wú)特定病原體級(jí)成年雄性SD大鼠隨機(jī)分為對(duì)照組(24只)、矽肺模型組(24只)、PolyG預(yù)防組(16只)和PolyG治療組(16只),采用一次性吸入式氣管滴注法,對(duì)照組大鼠予滅菌0.9%氯化鈉溶液1 mL,其余3組大鼠均予質(zhì)量濃度為50.0 g/L的矽塵混懸液1 mL以構(gòu)建矽肺纖維化大鼠模型。PolyG預(yù)防組大鼠于造模當(dāng)天,PolyG治療組大鼠于造模第28天,均一次性經(jīng)尾靜脈注射劑量為2.5 mg/kg體質(zhì)量的PolyG,于PolyG給藥后第28和56天各處死大鼠8只。觀察各組大鼠肺組織病理改變情況,以免疫印跡法測(cè)定葡萄糖調(diào)節(jié)蛋白-78(GRP78)、IRE1、CCAAT/增強(qiáng)子結(jié)合蛋白同源蛋白(CHOP)、半胱氨酸天冬氨酸蛋白酶(Casepase)-3、Casepase-12、Ⅰ型膠原和Ⅲ型膠原的蛋白相對(duì)表達(dá)水平。結(jié)果病理組織學(xué)檢查結(jié)果顯示:對(duì)照組大鼠肺組織結(jié)構(gòu)正常;矽肺模型組大鼠肺組織肺泡結(jié)構(gòu)破壞嚴(yán)重,出現(xiàn)纖維細(xì)胞性結(jié)節(jié)及大量膠原沉積;PolyG預(yù)防組和PolyG治療組大鼠矽結(jié)節(jié)及膠原沉積均較矽肺模型組減少。矽肺模型組大鼠肺組織中GRP78、IRE1、CHOP、Caspase-3、Caspase-12、Ⅰ型膠原和Ⅲ型膠原的蛋白相對(duì)表達(dá)水平均高于對(duì)照組(P0.05)。除PolyG預(yù)防組IRE1和CHOP外,PolyG預(yù)防組和治療組大鼠上述7個(gè)蛋白指標(biāo)的表達(dá)水平均低于矽肺模型組(P0.05),但仍高于對(duì)照組(P0.05)。造模后第56天,PolyG預(yù)防組GRP78、IRE1、Caspase-3、Caspase-12、Ⅰ型膠原和Ⅲ型膠原的蛋白相對(duì)表達(dá)水平均低于PolyG治療組(P0.05)。結(jié)論 IRE1介導(dǎo)的ERS未折疊蛋白反應(yīng)可能參與了PolyG干預(yù)大鼠矽肺纖維化的過程;PolyG可有效預(yù)防和治療矽肺纖維化,以預(yù)防性給藥效果更佳。
[Abstract]:Objective to investigate the role and mechanism of inositol demand kinase 1 (IRE1) -mediated endoplasmic reticulum stress (ER) induced apoptosis of (ERS) cells in rats with silicosis induced by polyguanosine monophosphate (PolyG). Methods Adult male SD rats were randomly divided into control group (n = 24), silicosis model group (n = 24) and PolyG treatment group (n = 16). Rats in the control group were given sterilizing 0.9% sodium chloride solution 1 mL, and the other three groups were given silica dust suspension of 50.0 g / L for 1 mL to establish silicosis fibrosis model. The rats in the PolyG prevention group were treated with the model on the same day. On the 28th day of model making, 8 rats in PolyG group were killed on the 28th and 56th day after administration of PolyG with PolyG, of 2.5 mg/kg body mass injected via caudal vein. The pathological changes of lung tissue in each group were observed. Glucose regulated protein-78 (GRP78), IRE1,CCAAT/ enhancer binding protein homologous protein (CHOP), caspase (Casepase) 3 and casepase-12 were determined by Western blot. The relative expression level of type I collagen and type 鈪，

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