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基质细胞衍生因子-1(SDF-1)表达增加通过促进骨髓间充质干细胞(BMSCs)迁移减轻哮喘大鼠气道炎症

[The increased expression of stromal cell-derived factor-1 (SDF-1) alleviates airway inflammation in asthmatic rats by promoting the migration of bone marrow mesenchymal stem cells (BMSCs)].

作者信息

Zhu Huizhi, Wang Kun, Zhu Shunzhi, Wang Dawei, Liu Xiangguo

机构信息

Department of Respiratory Diseases, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China. *Corresponding author, E-mail:

Graduate School, Anhui University of Traditional Chinese Medicine, Hefei 230012, China.

出版信息

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2023 Mar;39(3):213-219.

PMID:36946345
Abstract

Objective To observe the correlation of stromal cell-derived factor 1 (SDF-1) with bone marrow mesenchymal stem cell (BMSCs) migration and airway inflammation in asthmatic rats. Methods Twenty-four clean SD rats were randomly divided into normal control (NC) group, model control (MC) group, and BMSCs group. Asthma model was established by OVA. In the BMSCs group, 1×10 BMSCs (1 mL) were transplanted into the tail vein on the day the model was completed. Pathological changes in lung tissues were evaluated by HE staining. The count of inflammatory cells in bronchoalveolar lavage fluid(BALF) was evaluated by Wright-Giemsa staining. The concentrations of IL-4, IL-5, IL-13, IgE, IgG1 and IgG2a in BALF were tested by ELISA. The expression of SDF-1 and STAT6 mRNA in lung tissue was measured by real time quantitative PCR. The expression of SDF-1 protein in bronchial epithelial cells were evaluated by Immunofluorescence staining. The expression of SDF-1 and STAT6 protein in lung tissue were measured by Western blot analysis. Results Compared with the normal group, the number of relative inflammatory cell counts and the concentrations of IL-4, IL-5, IL-13, IgE, IgG1, and IgG2a in BALF of the MC group increased significantly. The mRNA and protein expression of SDF-1 and STAT6 in lung tissue increased significantly. Compared with the MC group, inflammatory cells and inflammatory cytokines of BALF of BMSCs group were decreased in numbers, as was the expression of SDF-1 and STAT6 in lung tissues. Compared with the MC group, the expression of SDF-1 gene in lung tissues was increased, as was the expression of SDF-1 protein in bronchial epithelial cells. Conclusion In the process of asthmatic inflammation, the expression of chemokine SDF-1 in the damaged site increases, and promotes the migration of exogenous BMSCs to the lung tissue of asthmatic rats. BMSCs can regulate immune imbalance of Th1/Th2 cells by homing to damaged lung tissue, thus inhibiting asthmatic airway inflammation.

摘要

目的 观察基质细胞衍生因子1(SDF-1)与哮喘大鼠骨髓间充质干细胞(BMSCs)迁移及气道炎症的相关性。方法 将24只清洁级SD大鼠随机分为正常对照组(NC组)、模型对照组(MC组)和BMSCs组。采用卵清蛋白(OVA)建立哮喘模型。在BMSCs组,于造模成功当天经尾静脉移植1×10⁶ BMSCs(1 mL)。通过HE染色评估肺组织病理变化。采用瑞氏-吉姆萨染色评估支气管肺泡灌洗液(BALF)中炎性细胞计数。采用酶联免疫吸附测定(ELISA)检测BALF中白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、白细胞介素-13(IL-13)、免疫球蛋白E(IgE)、免疫球蛋白G1(IgG1)和免疫球蛋白G2a(IgG2a)的浓度。采用实时定量聚合酶链反应(PCR)检测肺组织中SDF-1和信号转导及转录激活因子6(STAT6)mRNA的表达。采用免疫荧光染色评估支气管上皮细胞中SDF-1蛋白的表达。采用蛋白质免疫印迹法检测肺组织中SDF-1和STAT6蛋白的表达。结果 与正常组相比,MC组BALF中炎性细胞相对计数及IL-4、IL-5、IL-13、IgE、IgG1和IgG2a浓度显著增加。肺组织中SDF-1和STAT6的mRNA及蛋白表达显著增加。与MC组相比,BMSCs组BALF中炎性细胞和炎性细胞因子数量减少,肺组织中SDF-1和STAT6的表达也减少。与MC组相比,肺组织中SDF-1基因表达增加,支气管上皮细胞中SDF-1蛋白表达也增加。结论 在哮喘炎症过程中,趋化因子SDF-1在损伤部位的表达增加,促进外源性BMSCs向哮喘大鼠肺组织迁移。BMSCs可通过归巢至损伤的肺组织调节Th1/Th2细胞免疫失衡,从而抑制哮喘气道炎症。

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