[1]高璐阳 金旗 张毅 李欣 黄志华 章思铖 段安琪 赵智慧 赵青 罗勤 柳志红.PI3K/Akt/FoxO1信号通路对人源肺动脉平滑肌细胞及肺动脉高压大鼠细胞凋亡的影响[J].心血管病学进展,2024,(1):79.[doi:10.16806/j.cnki.issn.1004-3934.2024.01.020]
　GAO Luyang,JIN Qi,ZHANG Yi,et al.Effect of PI3K/Akt/FoxO1 Signaling Pathway on Apoptosis in Human Pulmonary Artery Smooth Muscle Cell and Pulmonary Hypertension Rat[J].Advances in Cardiovascular Diseases,2024,(1):79.[doi:10.16806/j.cnki.issn.1004-3934.2024.01.020]
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PI3K/Akt/FoxO1信号通路对人源肺动脉平滑肌细胞及肺动脉高压大鼠细胞凋亡的影响()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年1期
页码:
79
栏目:
论著
出版日期:
2024-02-21

文章信息/Info

Title:
Effect of PI3K/Akt/FoxO1 Signaling Pathway on Apoptosis in Human Pulmonary Artery Smooth Muscle Cell and Pulmonary Hypertension Rat
作者:
高璐阳1 金旗 1; 2 张毅 1; 3 李欣1 黄志华 1 章思铖1 段安琪1 赵智慧1 赵青1 罗勤1 柳志红1
（国家心血管病中心 中国医学科学院阜外医院 肺血管病中心,北京100037;2. 复旦大学附属中山医院 上海市心血管病研究所心内科,上海 200032;3. 电子科技大学附属四川省人民医院重症监护科,四川 成都 610072)
Author(s):
GAO Luyang1; JIN Qi1; 2; ZHANG Yi1; 3; LI Xin1; HUANG Zhihua1; ZHANG Sicheng1; DUAN Anqi1; ZHAO Zhihui1; ZHAO Qing1; LUO Qin1; LIU Zhihong1
(1.Center for Pulmonary Vascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences,National Center for Cardiovascular Diseases,Beijing 100037,China; 2. Department of Cardiology,Shanghai Institute of Cardiovascular Diseases,Zhongshan Hospital,Fudan University,Shanghai 200032,China; 3. Department of ICU,Sichuan Provincial People’s Hospital,University of Electronic Science and Technology of China, Chengdu 610072, Sichuan,China)
关键词:
肺动脉高压; PI3K/Akt/FoxO1信号通路; 肺动脉平滑肌细胞; 细胞凋亡
Keywords:
Pulmonary hypertension; PI3K/Akt/FoxO1 signaling pathway; Pulmonary artery smooth muscle cell; Cell apoptosis
DOI:
10.16806/j.cnki.issn.1004-3934.2024.01.020
摘要:
目的 探究磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/叉头框蛋白O1（FoxO1）信号通路对人源肺动脉平滑肌细胞（hPASMC）及肺动脉高压大鼠细胞凋亡的影响。 方法 细胞实验部分，将hPASMC分为4组：（1）空白对照组；（2）血小板源性生长因子-BB（PDGF-BB）组；（3）PDGF-BB+LY294002组；（4）PDGF-BB+紫杉醇（paclitaxel）组。采用TUNEL检测细胞凋亡，采用免疫印迹（Western blot）检测Bcl-2、裂解的胱天蛋白酶-3（cleaved caspase-3）和PI3K/Akt/FoxO1信号通路相关蛋白表达水平。动物实验部分，将12只SD大鼠随机分为4组：（1）空白对照组；（2）野百合碱（MCT）组；（3）MCT+LY294002组；（4）MCT+paclitaxel组。采用Western blot检测Bcl-2、cleaved caspase-3和PI3K/Akt/FoxO1信号通路相关蛋白表达水平。 结果 细胞实验部分：相比于PDGF-BB组，PDGF-BB+LY294002组与PDGF-BB+paclitaxel组的Bcl-2表达水平下降（P＜0.01），cleaved caspase-3表达水平上升（P＜0.01）；相比于空白对照组，PDGF-BB+LY294002组与PDGF-BB+paclitaxel组的凋亡率上升（P＜0.01）。动物实验部分：相比于MCT组，MCT+LY294002组与MCT+paclitaxel组Bcl-2、磷酸化Akt与磷酸化FoxO1表达水平下降（P＜0.01），cleaved caspase-3与FoxO1表达水平上升（P＜0.01）。各组之间PI3K表达水平无显著差异。 结论 PI3K/Akt/FoxO1信号通路抑制人源肺动脉平滑肌与肺动脉高压大鼠肺组织的细胞凋亡。
Abstract:
Objective To investigate the effects of phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O1(FoxO1) signaling pathway on human pulmonary artery smooth muscle cell(hPASMC) and pulmonary hypertension rat. Methods In cell experiment section,hPASMC was divided into 4 groups:(1)blank control group;(2)platelet-derived growth factor-BB(PDGF-BB) group;(3)PDGF-BB+LY294002 group;(4)PDGF-BB+paclitaxel group. Cell apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,the expression levels of Bcl-2,cleaved caspase-3 and PI3K/Akt/FoxO1 signaling pathway-related proteins were determined using Western blot. In animal experiment section,12 SD rats were randomly divided into 4 groups:(1)blank control group;(2)monocrotaline(MCT) group;(3)MCT+LY294002 group;(4)MCT+paclitaxel group. The expression levels of Bcl-2,cleaved caspase-3 and PI3K/Akt/FoxO1 signaling pathway-related proteins were evaluated using Western blot. Results In the cellular experiments,compared to the PDGF-BB group,the PDGF-BB+LY294002 group and PDGF-BB+paclitaxel group showed the decreased expression levels of Bcl-2(P<0.01),and the increased expression levels of cleaved caspase-3(P<0.01). Compared to the blank control group,the PDGF-BB+LY294002 group and PDGF-BB+paclitaxel group showed the increased apoptosis rates(P<0.01). In the animal experiments,compared to the MCT group,the MCT+LY294002 group and MCT+paclitaxel group showed the decreased expression levels of Bcl-2, phosphorylated Akt and phosphorylated FoxO1(P<0.01),and the increased expression levels of cleaved caspase-3 and FoxO1(P<0.01),with no significant difference in PI3K expression levels between the groups. Conclusion The PI3K/Akt/FoxO1 signaling pathway inhibits cell apoptosis in hPASMC and lung tissue of pulmonary hypertension rat.

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更新日期/Last Update: 2024-03-06