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目的探讨Sonic hedgehog(SHH)信号通路在脂多糖(LPS)诱导的急性肺损伤(ALI)中的表达变化及意义。方法实验动物随机分为对照组、5 mg/kg LPS处理组、50 mg/kg环巴胺处理组。HE染色观察肺组织病理改变,测定肺湿干质量比值(W/D),反转录PCR检测肺组织肿瘤坏死因子α(TNF-α)及SHH、Patched(PTC)及下游转录因子GLI1的mRNA表达,Western blot法检测肺组织SHH和GLI1的蛋白表达。结果 LPS处理组肺组织病理损伤评分、W/D、TNF-αmRNA表达水平明显高于对照组。LPS处理组SHH、PTC、GLI1的mRNA表达水平,在6 h与对照组相比,无明显差异,LPS处理12、24 h时表达水平明显高于对照组,与时间呈正相关。与对照组相比,LPS处理组6、12、24 h的SHH、GLI1蛋白表达水平均明显升高,且与时间呈正相关。环巴胺处理后,SHH、PTC、GLI1的mRNA表达及SHH、GLI1的蛋白表达水平均降低,同时肺组织病理损伤评分、W/D及TNF-αmRNA表达均高于LPS处理组。结论 LPS所致ALI的发展过程中存在SHH信号通路的激活,且SHH信号通路相关分子表达上调,可减轻肺损伤参与肺组织损伤后修复。
Objective To investigate the changes and significance of Sonic hedgehog (SHH) signaling pathway in acute lung injury induced by lipopolysaccharide (LPS). Methods Experimental animals were randomly divided into control group, 5 mg / kg LPS treatment group and 50 mg / kg cyclopamine treatment group. The pathological changes of lung tissue were observed by HE staining, the wet / dry weight ratio (W / D) of lung was measured, and the mRNA expressions of tumor necrosis factor-α (TNF-α), SHH, Patched (PTC) and GLI1 Expression and Western blot were used to detect the protein expression of SHH and GLI1 in lung tissue. Results The lung injury scores, W / D and TNF-αmRNA expression in LPS group were significantly higher than those in control group. The mRNA expression of SHH, PTC and GLI1 in LPS treatment group had no significant difference at 6 h compared with that in control group. The expression level of SHP, PTC and GLI1 at LPS treatment group was significantly higher than that of control group at 12 and 24 h, which was positively correlated with time. Compared with the control group, the expression of SHH and GLI1 protein in LPS treatment group at 6, 12 and 24 h were significantly increased, and positively correlated with time. After cyclopamine treatment, the mRNA expression of SHH, PTC and GLI1 and the protein expression of SHH and GLI1 decreased, while the pathological damage scores, W / D and TNF-αmRNA expression in lung tissue were higher than those in LPS group. Conclusion The activation of SHH signaling pathway during the development of ALI induced by LPS may be related to the up-regulation of SHH signaling pathway-related molecules, which may reduce the involvement of lung injury in the repair of lung injury.