格列本脲抑制NLRP3炎性小体活化对肺动脉平滑肌细胞增殖与迁移的影响  

Glyburide prevents pulmonary artery smooth muscle cell proliferation and migration via inhibiting NLRP3 activation

作　　者：刘亚飞[1] 王望[1] 柳婷[1] 张炜[1] 刘杰[1] 王军[1] Liu Yafei Wang Wang Liu Ting Zhang Wei Liu Jie Wang Jun(Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China)

机构地区：[1]首都医科大学基础医学院生理学教研室,北京100069

出　　处：《中华结核和呼吸杂志》2017年第6期440-444,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：基金项目：国家自然科学基金（81370152,31600939,81270117）;北京市自然科学基金（7142027）;北京市优秀人才青年骨干个人项目（2015000020124G111）

摘　　要：目的探讨格列本脲是否通过抑制NLRP3炎性小体活化缓解肺动脉平滑肌细胞（PASMCs）增殖与迁移。方法传代培养人PASMCs并分为4组：对照组、格列本脲组、血小板源性生长因子（PDGF）组和PDGF＋格列本脲组，实验组分别给予格列本脲干预和PDGF诱导PASMCs增殖和迁移。采用Western blot法检测各组细胞中NLRP3炎性小体的活化状况，噻唑蓝法检测细胞增殖率，Transwell法检测细胞迁移能力。结果PDGF组与对照组相比NLRP3表达升高至（1.38±0.09，t＝3.998, P〈0.001）；半胱氨酸蛋白酶-1（caspase-1）表达增加到（1.32±0.10，t＝3.268, P〈0.01）；IL-1β表达上调为（1.43±0.19，t＝2.096, P〈0.05）。与对照组相比，格列本脲不影响NLRP3、caspase-1和IL-1β表达；PDGF＋格列本脲组与PDGF组相比NLRP3的表达降低（20.5±7.6）% （t＝2.862, P〈0.01），caspase-1表达减少（32.9±3.4）% （t＝4.154, P〈0.001），IL-1β表达下调（24.7±5.3）% （t＝2.335, P〈0.05）。与对照组相比，PDGF组PASMCs增殖升高至（1.74±0.23，t＝4.717, P〈0.001），迁移增加到（3.12±0.8，t＝5.249, P〈0.001）。与对照组相比，格列本脲不影响PASMCs的增殖与迁移；但可明显抑制PDGF诱导的PASMCs的增殖（50.5±4.3）% （t＝4.462, P〈0.001）和迁移（42.77±2.84）% （t＝3.716, P〈0.001）。结论格列本脲可通过抑制NLRP3炎性小体的活化缓解PDGF诱导的PASMCs增殖与迁移。Objective To investigate whether glyburide prevents platelet-derived growth factor （PDGF） induced pulmonary artery smooth muscle cells（PASMCs） proliferation and migration via inhibiting nucleotide binding domain leucine-rich repeat-containing receptors protein 3（NLRP3） inflammasome activation.Methods PASMCs were divided into 4 groups： control group, glyburide group, PDGF group and PDGF＋ glyburide group. Cell proliferation and migration were assessed by MTT and Transwell respectively. The NLRP3 inflammasome activation was assessed by Western blot.Results Compared with the control group, the protein expressions of NLRP3, caspase-1 and IL-1β in PASMCs were increased to （1.38±0.09, t=3.998, P〈0.001）, （1.32±0.1, t=3.268, P〈0.01）and（1.43±0.19） （t=2.096, P〈0.05） folds in the PDGF group. Glyburide had no effect on NLRP3, caspase-1 and IL-1β expression as compared with the control group, while the NLRP3, caspase-1 and IL-1β were decreased by（20.49±7.6）% （t=2.862, P〈0.01）, （32.94±3.44）% （t=4.154, P〈0.001） and （24.67±5.29）% （t=2.335, P〈0.05） in the PDGF＋ glyburide group, respectively, as compared with the PDGF group. Compared with the control group, the PASMCs proliferation and migration in the PDGF group were significantly increased to （1.74±0.23, t=4.717, P〈0.001） and （3.12±0.8, t=5.249, P〈0.001） folds, respectively. Compared with the control group, glyburide had no effect on PASMCs proliferation and migration. In PDGF＋ glyburide group, cell proliferation was reduced by （50.5±4.27）% （t=4.462, P〈0.001） and cell migration count was lower than in the PDGF group （42.77±2.84）% （t=3.716, P〈0.001）.Conclusion Glyburide could ameliorate PDGF-induced PASMCs proliferation and migration by inhibiting NLRP3 inflammasome activation.

关 键 词：格列本脲 血小板源性生长因子 肌细胞 平滑肌 NLRP3 

分 类 号：R544.1[医药卫生—心血管疾病]