摘要
目的探讨多囊蛋白-1(PC-1)在急性主动脉夹层(AD)发病机制中的作用及分子机制。方法收集2019年10月至2020年1月于郑州大学第一附属医院行主动脉弓置换术的6例急性AD患者的病变主动脉组织标本作为AD组,另选择6例非主动脉疾病的器官捐赠者的正常主动脉组织标本作为对照组。采用Western blot法检测主动脉组织中PC-1、凋亡相关蛋白及磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号通路相关蛋白的磷酸化位点的表达,SM22α免疫荧光/DNA末端转移酶介导的dUTP缺口末端标记法双标染色法检测主动脉平滑肌细胞(VSMC)凋亡情况。结果对照组和AD组受试者主动脉组织中PC-1蛋白的相对表达量分别为1.00±0.07和0.72±0.04,AD组受试者主动脉组织中PC-1蛋白的相对表达量显著低于对照组(t=7.614,P<0.01)。对照组和AD组受试者主动脉VSMC凋亡的荧光强度分别为59.03±4.57和71.26±8.25,AD组受试者主动脉VSMC凋亡的荧光强度显著高于对照组(t=3.178,P<0.05)。AD组受试者主动脉组织中cleaved caspase-3、cleaved caspase-7、cleaved caspase-9、Bax蛋白相对表达量显著高于对照组(P<0.01),AD组受试者主动脉组织中Bcl-2蛋白相对表达量显著低于对照组(P<0.01)。AD组受试者主动脉组织中PI3K的p85、p110β磷酸化位点及Akt的p-Ser-Akt、p-Thr-Akt磷酸化位点的相对表达量显著低于对照组(P<0.01)。结论AD患者主动脉组织中PC-1蛋白表达降低,PC-1蛋白低表达可能通过抑制PI3K/Akt信号通路活化、提高促凋亡蛋白表达及降低抗凋亡蛋白表达促进VSMC凋亡,这可能是AD发病的潜在机制之一。
Objective To investigate the role and molecular mechanism of polycystin-1(PC-1)in the pathogenesis of acute aortic dissection(AD).Methods The diseased aortic tissue samples of six patients with acute AD who underwent aortic arch replacement in the First Affiliated Hospital of Zhengzhou University from October 2019 to January 2020 were collected as the AD group,and the normal aortic tissue samples of six organ donors without aortic disease were selected as the control group.The expressions of PC-1,apoptosis related proteins and phosphorylation sites of phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signal pathway related proteins were detected by Western blot.The vascular smooth muscle cell(VSMC)apoptosis was detected by SM22αimmunofluorescence/TdT-mediated biotinylated-dUTP nick end labeling double staining.Results The relative expression of PC-1 protein in the aortic tissues of subjects in the control group and AD group was 1.00±0.07 and 0.72±0.04,respectively.The relative expression of PC-1 protein in aortic tissues of subjects in the AD group was significantly lower than those in the control group(t=7.614,P<0.01).The fluorescence intensity of VSMC apoptosis of subjects in the control group and AD group was 59.03±4.57 and 71.26±8.25,respectively.The fluorescence intensity of VSMC apoptosis of subjects in the AD group was significantly higher than that in the control group(t=3.178,P<0.05).The relative expressions of cleaved caspase-3,cleaved caspase-7,cleaved caspase-9 and Bax protein in aortic tissues of subjects in the AD group were significantly higher than those in the control group(P<0.01).The relative expression of Bcl-2 protein in aortic tissues of subjects in the AD group was significantly lower than that in the control group(P<0.01).The relative expressions of PI3K phosphorylation sites p85,p110βand Akt phosphorylation sites p-Ser-Akt,p-Thr-Akt in aortic tissues of subjects in the AD group were significantly lower than those in the control group(P<0.01).Conclusion The expression of PC-1 protein was decreased in the aortic tissues of AD patients.The low expression of PC-1 protein may promote the apoptosis of VSMC by inhibiting the activation of PI3K/Akt signal pathway,increasing the expression of pro-apoptotic protein and decreasing the expression of anti-apoptotic protein,which may be one of the potential mechanisms of AD.
作者
王蕾
崔立坤
张琳
刘娜
WANG Lei;CUI Likun;ZHANG Lin;LIU Na(Department of Emergency,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,Henan Province,China)
出处
《新乡医学院学报》
CAS
2023年第1期35-39,共5页
Journal of Xinxiang Medical University
基金
2019年度河南省重点研发与推广专项(科技攻关)(编号:192102310060)。
