整合素α_(5)β_(1)表达下调参与人急性A型主动脉夹层形成  被引量:1

Down-regulation of integrinα_(5)β_(1) participates in the formation of acute type A aortic dissection in human

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作  者:薛明明 杨依霖 邢玲玉 徐斐翔 汪升 陈玉梅 陈斌 宋振举 姚晨玲 顾国嵘 童朝阳 XUE Ming-ming;YANG Yi-lin;XING Ling-yu;XU Fei-xiang;WANG Sheng;CHEN Yu-mei;CHEN Bin;SONG Zhen-ju;YAO Chen-ling;GU Guo-rong;TONG Chao-yang(Department of Emergency,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区:[1]复旦大学附属中山医院急诊科,上海200032

出  处:《中国临床医学》2023年第2期265-271,共7页Chinese Journal of Clinical Medicine

基  金:上海市科学技术委员会基金(21Y11902200);上海市卫生健康委员会基金(201940163)。

摘  要:目的探讨整合素α_(5)β_(1)在急性A型主动脉夹层(acute type A aortic dissection,AAAD)患者病变组织及人主动脉平滑肌细胞(human aortic smooth muscle cell,HASMC)中的表达情况及可能的调控机制。方法免疫组织化学检测AAAD患者病变组织整合素α_(5)β_(1)、磷酸化黏着斑激酶(phosphorylated focal adhesion kinase,p-FAK)和Caspase 3的蛋白表达水平。免疫荧光检测HASMC中整合素α_(5)β_(1)、p-FAK的表达。siRNA下调HASMC中整合素α_(5)β_(1)的表达水平,CCK-8实验检测HASMC的增殖活力,流式细胞仪检测HASMC细胞凋亡。结果免疫组化检测结果显示,与正常组织相比,AAAD患者病变组织整合素α_(5)β_(1)表达下降(P<0.05)。免疫荧光检测结果显示,正常HASMC中,整合素α_(5)β_(1)和FAK定位于相同部位。转染siRNA下调整合素α_(5)β_(1)的表达后,HASMC增殖减少、凋亡增加(P<0.001),整合素α_(5)β_(1)及p-FAK蛋白的表达下调(P<0.001)。结论AAAD患者病变组织整合素α_(5)β_(1)/FAK信号通路表达抑制;体外抑制该信号通路可导致HASMC细胞增殖减少、凋亡增加。Objective To explore expression levels of integrinα_(5)β_(1)in lesion tissues of patients with acute type A aortic dissection(AAAD)and human aortic smooth muscle cells(HASMC)and the possible regulatory mechanism.Methods Immunohistochemistry was used to detect expression levels of integrinα_(5)β_(1),phosphorylated focal adhesion kinase(p-FAK)and Caspase 3 proteins in the lesion tissues of AAAD patients.Immunofluorescence was used to detect integrinsα_(5)β_(1)and p-FAK expressions in HASMC.siRNA was used to downregulate integrinα_(5)β_(1)in HASMC,CCK-8 and flow cytometry were used to detect the proliferation activity and apoptosis of HASMC,respectively.Results The expression of integrinα_(5)β_(1)at lesion tissues in AAAD patients was decreased(P<0.05).Integrinsα_(5)β_(1)and FAK expressed in the same sites of normal HASMC.After down regulating expression of integrinα_(5)β_(1)in HASMC,the smooth muscle cells showed decreased proliferation and increased apoptosis(P<0.001).The expression ofα_(5)β_(1)and FAK proteins was downregulated(P<0.001).Conclusions Integrinα_(5)β_(1)/FAK signal pathway in the aorta of AAAD patients is down regulated,and the HASMC proliferation decreases and apoptosis increases after this signal pathway is inhibited.

关 键 词:整合素α_(5)β_(1) 急性A型主动脉夹层 主动脉平滑肌细胞 

分 类 号:R543.1[医药卫生—心血管疾病]

 

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