HSF1对LPS诱导的急性肺损伤小鼠的保护作用及其相关差异表达基因的筛选

发布时间：2018-06-17 05:12

  本文选题：急性肺损伤 + 热休克因子　； 参考：《中国病理生理杂志》2017年11期

【摘要】：目的:探讨热休克因子1(heat shock factor 1,HSF1)减轻脂多糖(lipopolysaccharide,LPS)诱导的小鼠急性肺损伤的作用及其分子机制。方法:采用气管滴注LPS的方法制备小鼠急性肺损伤模型,观察HSF1野生型小鼠(HSF1~(+/+))和HSF1敲除小鼠(HSF1~(-/-))肺大体改变和肺组织病理改变,检测支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中总蛋白、血管内皮生长因子(vascular endothelial growth factor,VEGF)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β和IL-6的蛋白表达。采用基因芯片技术筛选经LPS处理后的HSF1~(+/+)和HSF1~(-/-)小鼠肺组织中的差异表达基因,并进一步采用real-time PCR对CXC趋化因子受体2(CXC chemokine receptor 2,CXCR2)的表达进行验证。结果:与经LPS刺激后的HSF1~(+/+)小鼠相比,经LPS刺激的HSF1~(-/-)小鼠肺大体和病理损伤加重,BALF中总蛋白、VEGF、TNF-α、IL-1β和IL-6的含量升高,差异具有统计学意义(P0.05)。基因芯片分析发现,与经LPS处理的HSF1~(+/+)小鼠相比,HSF1~(-/-)小鼠共筛选出918个差异基因,有65个基因表达差异明显,其中Atg7、ccr1、cxcr2、Tbl1xr1、Mmp9、Pparg、Plcb2、Arrb2、Cntn1、Col4a6等共28个基因在HSF1~(-/-)小鼠的肺组织中表达明显上调;Fgfr1、Fgfr2、Map4k4、Ddx58、Tfg、Stat3、Smad4、Lamc1、Sdc3等共37个基因表达明显下调。Real-time PCR结果显示,CXCR2的mRNA水平在LPS刺激的HSF1~(-/-)小鼠肺组织较HSF1~(+/+)小鼠表达明显上调,表达趋势与基因芯片结果一致。结论:HSF1能减轻LPS诱导的小鼠急性肺损伤,CX-CR2可能参与了对肺组织的保护作用。
[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- 伪 (TNF- 伪), 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- 伪 TNF- 伪 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绛夊叡28涓�鍩哄洜鍦℉SF1~(-/-)灏忛紶鐨勮偤缁勭粐涓�琛ㄨ揪鏄庢樉涓婅埃�

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