本文選題：急性肺損傷 + 熱休克因子��； 參考：《中國病理生理雜志》2017年11期

【摘要】：目的:探討熱休克因子1(heat shock factor 1,HSF1)減輕脂多糖(lipopolysaccharide,LPS)誘導(dǎo)的小鼠急性肺損傷的作用及其分子機(jī)制。方法:采用氣管滴注LPS的方法制備小鼠急性肺損傷模型,觀察HSF1野生型小鼠(HSF1~(+/+))和HSF1敲除小鼠(HSF1~(-/-))肺大體改變和肺組織病理改變,檢測支氣管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中總蛋白、血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)、腫瘤壞死因子α(tumor necrosis factor-α,TNF-α)、白細(xì)胞介素(interleukin,IL)-1β和IL-6的蛋白表達(dá)。采用基因芯片技術(shù)篩選經(jīng)LPS處理后的HSF1~(+/+)和HSF1~(-/-)小鼠肺組織中的差異表達(dá)基因,并進(jìn)一步采用real-time PCR對CXC趨化因子受體2(CXC chemokine receptor 2,CXCR2)的表達(dá)進(jìn)行驗證。結(jié)果:與經(jīng)LPS刺激后的HSF1~(+/+)小鼠相比,經(jīng)LPS刺激的HSF1~(-/-)小鼠肺大體和病理損傷加重,BALF中總蛋白、VEGF、TNF-α、IL-1β和IL-6的含量升高,差異具有統(tǒng)計學(xué)意義(P0.05)�；蛐酒治霭l(fā)現(xiàn),與經(jīng)LPS處理的HSF1~(+/+)小鼠相比,HSF1~(-/-)小鼠共篩選出918個差異基因,有65個基因表達(dá)差異明顯,其中Atg7、ccr1、cxcr2、Tbl1xr1、Mmp9、Pparg、Plcb2、Arrb2、Cntn1、Col4a6等共28個基因在HSF1~(-/-)小鼠的肺組織中表達(dá)明顯上調(diào);Fgfr1、Fgfr2、Map4k4、Ddx58、Tfg、Stat3、Smad4、Lamc1、Sdc3等共37個基因表達(dá)明顯下調(diào)。Real-time PCR結(jié)果顯示,CXCR2的mRNA水平在LPS刺激的HSF1~(-/-)小鼠肺組織較HSF1~(+/+)小鼠表達(dá)明顯上調(diào),表達(dá)趨勢與基因芯片結(jié)果一致。結(jié)論:HSF1能減輕LPS誘導(dǎo)的小鼠急性肺損傷,CX-CR2可能參與了對肺組織的保護(hù)作用。
[Abstract]:Aim: to investigate the effect of heat shock factor 1(heat shock factor 1 (HSF1) on acute lung injury induced by lipopolysaccharide (LPS) in mice and its molecular mechanism. Methods: the acute lung injury model was established by endotracheal instillation of lipopolysaccharide (LPS) in mice. The gross changes of the lung and the pathological changes of lung tissue were observed in wild HSF1 mice and HSF1 knockout mice. The total protein of bronchoalveolar lavage fluidBALFwas detected in bronchoalveolar lavage fluid (bronchoalveolar lavage fluidBALF). Vascular endothelial growth factor (endothelial growth), vascular endothelial growth factor (endothelial growth), tumor necrosis factor- 偽 (TNF- 偽), interleukin (IL) interleukin-1 尾 and interleukin-6 (IL-6). The differentially expressed genes in the lung tissues of lipopolysaccharide treated mice were screened by DNA chip technique, and the expression of CXC chemokine receptor 2CXC chemokine receptor 2CXCR2 was further verified by real-time PCR. Results: compared with lipopolysaccharide (LPS) stimulated HSF1 mice, the lung gross and pathological injury in LPS-stimulated HSF1TNF- 偽 TNF- 偽 IL-1 尾 and IL-6 increased significantly (P 0.05). Gene chip analysis showed that 918 differentially expressed genes were screened out in HSF1- / -mices compared with those treated with LPS, and 65 of them showed significant differences in gene expression. 鍏朵腑Atg7,ccr1,cxcr2,Tbl1xr1,Mmp9,Pparg,Plcb2,Arrb2,Cntn1,Col4a6絳夊叡28涓熀鍥犲湪HSF1~(-/-)灝忛紶鐨勮偤緇勭粐涓〃杈炬槑鏄句笂璋，

本文編號：2029864