HSG通过Wnt/β-catenin通路抑制COPD大鼠气道成纤维细胞增殖

Objective To study the relationship between the hyperplasia suppressor gene (HSG) and the Wnt/β-catenin signaling pathway in airway remodeling in rats with chronic obstructive pulmonary disease (COPD) and its mechanism of regulating airway remodeling. Methods Rats were randomly divided into a control group and a COPD model group. The model group was established by intratracheal injection of lipopolysaccharide combined with smoking. COPD tissues were identified by HE staining, and the total area of the airway wall / the perimeter of the airway basement membrane (WAt/Pbm) was measured to evaluate the airway remodeling. Rat airway fibroblasts were cultured by the tissue explant adherence method. The expressions of HSG and β-catenin mRNAs in fibroblasts were detected by real-time PCR. The protein expressions of HSG, β-catenin, GSK - 3β, TGF - β1 and MMP - 9 were detected by Western blot combined with ELISA. The correlations between the expressions of HSG and β-catenin genes and the secretions of TGF - β1 and MMP - 9 cytokines were analyzed. Results The small airway remodeling in the model group was significant. The expressions of HSG mRNA and protein in the airway fibroblasts of COPD rats were lower than those in the control group. The expressions of β-catenin mRNA and protein were higher than those in the control group, and the protein expressions of P - GSK - 3β, TGF - β1 and MMP - 9 were also higher than those in the control group. The expression of HSG mRNA was negatively correlated with the expression of β-catenin mRNA and with the secretions of TGF - β1 and MMP - 9 cytokines. Conclusion HSG may participate in airway remodeling by regulating the Wnt/β-catenin signaling pathway and inhibiting the proliferation of rat airway fibroblasts.

目的 研究增殖抑制基因(HSG) 在大鼠慢性阻塞性肺疾病( COPD) 气重建中与 Wnt/β-catenin 信号传导通路的关系及其调控气道重建的机制。方法 将大鼠随机分为对照组及 COPD 模型组，模型组采用气道内注射脂多糖加烟熏方法建立。HE 染色鉴定 COPD 组织，测定气道管壁总面积 /气道基底膜周长( WAt/Pbm) 评价气道重建情况。组织块贴壁法培养大鼠气道成纤维细胞，real time-PCＲ检测成纤维细胞 HSG 和 β-catenin mＲNA 表达。West-ern blot 联合 ELISA 法检测 HSG、β-catenin、GSK-3β、TGF-β1 和 MMP-9 蛋白表达。分析 HSG、β-catenin 基因表达与TGF-β1和 MMP-9 细胞因子分泌的相关性。结果 模型组大鼠小气道重建显著。COPD 大鼠气道成纤维细胞中HSG mＲNA 和蛋白表达均低于对照组。β-catenin mＲNA 和蛋白表达均高于对照组，P-GSK-3β、TGF-β1 和 MMP-9蛋白表达也高于对照组。HSG mＲNA 的表达与 β-catenin mＲNA 表达及与 TGF-β1 和 MMP-9 细胞因子分泌呈负相关。结论 HSG 可能通过调控 Wnt/β-catenin信号通路，抑制大鼠气道成纤维细胞的增殖从而参与气道重建。