黄芩素对哮喘小鼠气道平滑肌细胞增殖、迁移及JAK/STAT通路的影响  

Effects of baicalein on proliferation, migration and JAK/STAT pathway of airway smooth muscle cells in asthmatic mice

作　　者：余保 申严[1] 卓宋明[1] Yu Bao;Shen Yan;Zhuo Songming(Department of Respiratory and Critical Care Medicine,Shenzhen Longgang Central Hospital,Shenzhen 518000,China)

机构地区：[1]深圳市龙岗中心医院呼吸与危重症医学科,深圳518000

出　　处：《广西医科大学学报》2021年第9期1692-1697,共6页Journal of Guangxi Medical University

基　　金：深圳市龙岗区经济与科技发展专项资金—医疗卫生科技计划项目(No.LGKCYLWS2019000962)。

摘　　要：目的:探究黄芩素对哮喘小鼠气道平滑肌细胞(ASMCs)增殖、迁移及Janus蛋白酪氨酸激酶(JAK)/信号转导和转录活化蛋白(STAT)通路的影响。方法:取小鼠原代ASMCs进行分离与培养,采用重组小鼠血小板衍生生长因子(PDGF)诱导小鼠ASMCs增殖,分别加入不同浓度的黄芩素(0μmol/L、10μmol/L、20μmol/L、40μmol/L)。另设对照组、JAK/STAT信号通路激活剂白介素6(IL-6)与黄芩素联用组(50 ng/ml的IL-6和40μmol/L的黄芩素),于培养箱中继续培养48 h。MTT法检测ASMCs增殖情况;划痕愈合实验检测ASMCs迁移能力;酶联免疫吸附法(ELISA)检测各组细胞培养上清中IL-6、IL-8水平;蛋白免疫印迹(western blot)检测JAK2、STAT3及其磷酸化蛋白表达。结果:与对照组相比,PDGF组细胞增殖率、迁移率、IL-6、IL-8水平、p-JAK2/JAK2、p-STAT3/STAT3表达显著升高(P<0.05);与PDGF组相比,20μmol/L、40μmol/L黄芩素组细胞增殖率、迁移率、IL-6水平、IL-8水平、p-JAK2/JAK2、p-STAT3/STAT3表达明显降低(P<0.05);IL-6+40μmol/L黄芩素联用组能明显逆转黄芩素对ASMCs增殖、迁移及炎性因子、JAK2/STAT3通路的抑制作用(P<0.05)。结论:黄芩素可抑制哮喘小鼠气道平滑肌细胞的增殖和迁移,其作用机制可能与抑制JAK2/STAT3信号通路有关。Objective: To investigate the effect of baicalein on the proliferation, migration and Janus protein tyrosine kinase(JAK)/signal transducer and activator of transcription(STAT) pathway of airway smooth muscle cells(ASMCs) in asthmatic mice. Methods: Primary mouse ASMCs were isolated and cultured, the proliferation of ASMCs was induced by recombinant mouse platelet-derived growth factor(PDGF), then different concentrations of baicalein(0, 10, 20, 40 μmol/L) were added respectively, in addition, control group and JAK/STAT signal pathway activator interleukin-6(IL-6) combined with baicalein group(50 ng/mL IL-6 and 40 μmol/L baicalein) were set up, and the cells were cultured for 48 hours. MTT assay was used to detect the proliferation of ASMCs;scratch healing test was used to detect the migration ability of ASMCs;enzyme linked immunosorbent assay(ELISA) was used to detect the levels of IL-6 and IL-8 in cell culture supernatant;Western blot was used to detect the expression of JAK2, STAT3 and their phosphorylated protein levels. Results: Compared with the control group, the proliferation rate, migration rate, the levels of IL-6 and IL-8, p-JAK2/JAK2, and p-STAT3/STAT3 were significantly increased in PDGF group(P<0.05). Compared with PDGF group, the proliferation rate, migration rate, the levels of IL-6 and IL-8, p-JAK2/JAK2, and p-STAT3/STAT3 in 20 μmol/L and 40 μmol/L baicalein group were significantly decreased(P<0.05). IL-6+40 μmol/L baicalein significantly reversed the inhibitory effects of baicalein on proliferation, migration, inflammatory factors and JAK2/STAT3 pathway related protein levels in ASMCs(P<0.05). Conclusion: Baicalein can inhibit the proliferation and migration of airway smooth muscle cells in asthmatic mice, and its mechanism may be related to the inhibition of JAK2/STAT3 signaling pathway.

关 键 词：哮喘 黄芩素 气道平滑肌细胞 增殖 Janus蛋白酪氨酸激酶/信号转导和转录活化蛋白 

分 类 号：R963[医药卫生—微生物与生化药学]