文章摘要
孙德芳,孔 辉,解卫平,王 虹.Ripasudil对PDGF⁃BB诱导人肺动脉平滑肌细胞增殖和迁移的影响[J].南京医科大学学报,2018,(7):878~884
Ripasudil对PDGF⁃BB诱导人肺动脉平滑肌细胞增殖和迁移的影响
Effects of ripasudil on proliferation and migration of human pulmonary arterial smooth cells induced by platelet⁃derived growth factor⁃BB
投稿时间:2018-03-29  
DOI:10.7655/NYDXBNS20180703
中文关键词: ripasudil  肺动脉高压  Rho激酶  Rho激酶抑制剂
英文关键词: ripasudil  pulmonary arterial hypertension  Rho kinase  Rho kinase inhibitors
基金项目:国家科技重大专项(2015ZX10003001);江苏省卫生厅重点项目(H201601)
作者单位
孙德芳 南京医科大学第一附属医院呼吸与危重症学科江苏 南京 210029 
孔 辉 南京医科大学第一附属医院呼吸与危重症学科江苏 南京 210029 
解卫平 南京医科大学第一附属医院呼吸与危重症学科江苏 南京 210029 
王 虹 南京医科大学第一附属医院呼吸与危重症学科江苏 南京 210029 
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中文摘要:
      目的:研究Rho激酶抑制剂ripasudil对血小板源性生长因子(platelet?derived growth factor,PDGF)?BB诱导人肺动脉平滑肌细胞(human pulmonary arterial smooth cells,HPASMCs)增殖和迁移的影响及其相关机制。方法:培养HPASMCs,随机分为control组、PDGF?BB组、PDGF?BB+ripasudil组、ripasudil组。采用CCK?8法检测细胞活力;EdU掺入法检测HPASMCs增殖;Transwell实验检测HPASMCs迁移;Real?time PCR检测基质金属蛋白酶(matrix metalloproteinase,MMP)?2 mRNA表达;Western blot检测MMP?2蛋白表达以及肌球蛋白磷酸酶目标亚基1(myosin phosphatase target subunit 1,MYPT1)、细胞外调节蛋白激酶1/2(extracellar regulated protein kinases 1/2,ERK1/2)、p38激酶和蛋白激酶B(protein kinase B,PKB/Akt)的磷酸化。结果:与control组相比,ripasudil能显著抑制PDGF?BB诱导HPASMCs增殖及迁移(P<0.01),降低MMP?2 mRNA及蛋白的表达(P<0.05),下调MYPT1、ERK1/2、p38及Akt的磷酸化(P<0.05)。结论:Ripasudil抑制PDGF?BB诱导的HPASMCs增殖和迁移,可能与下调MYPT1、ERK1/2、p38及Akt的磷酸化有关。Ripasudil可能是治疗肺动脉高压的潜在药物。
英文摘要:
      Objective:To investigate the effects of ripasudil on proliferation and migration of human pulmonary arterial smooth cells(HPASMCs)induced by platelet?derived growth factor(PDGF)?BB and the mechanisms underlying. Methods:Cultured HPASMCs were divided into four groups:the control group,the PDGF?BB?treated group,the PDGF?BB and ripasudil?treated group and the ripasudil?treated group. CCK?8 was applied to investigate cell viability and EdU assay was used to evaluate the proliferation of HPASMCs. Transwell assay was employed to examine cell migration. The expression of matrix metalloproteinase?2(MMP?2)was determined by real?time PCR and Western blot. The levels of phosphorylated myosin phosphatase target subunit 1(MYPT1),extracellar regulated protein kinases 1/2(ERK1/2),p38,and protein kinase B(PKB/Akt)were detected by Western blot. Results:Compared with the control group,ripasudil blocked the proliferation and migration of HPASMCs challenged by PDGF?BB(P<0.01). Ripasudil suppressed PDGF?BB?induced upregulation of MMP?2(P<0.05). Moreover,ripasudil inhibited PDGF?BB?induced phosphorylation of MYPT1,ERK1/2,p38,and Akt(P<0.05). Conclusion:Ripasudil significantly inhibited PDGF?BB?induced proliferation and migration of HPASMCs,which might be attributed to the inhibition of MYPT1,ERK1/2,p38 and Akt. Ripasudil,a Rho kinase inhibitor,might be a potential therapeutic option in PAH.
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