过表达ACE2基因的骨髓间充质干细胞对肺动脉高压大鼠的干预作用

王俊贤; 马倍; 刘珍君; 肖梦媛; 余丽琴; 彭子健; 魏文燕; 姚峰; 陈建英

doi:10.13201/j.issn.1001-1439.2018.04.020

过表达ACE2基因的骨髓间充质干细胞对肺动脉高压大鼠的干预作用

- 1 广东医科大学附属医院老年病科(广东湛江, 524001);
- 2 广东医科大学附属医院心内科
基金项目:
国家自然科学基金项目 (N0:81370242)

广东省医学科研基金项目 (N0:A 2015278)

详细信息

通讯作者: 陈建英,E-mail:jychen271@126.com

中图分类号: R543.2

收稿日期: 2017-08-22

Therapeutic effect of bone marrow-derived mesenchymal stem cells overexpressing angiotensin-converting enzyme 2 on rat models of pulmonary arterial hypertension

- 1 Department of Geriatrics;
- 2 Department of Cardiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, China

More Information

Corresponding author: CHEN Jianyin, E-mail: jychen271@126.com

Received Date: 22 August 2017

摘要

摘要: 目的:探讨过表达血管紧张素转化酶2 (ACE2) 的大鼠骨髓间充质干细胞 (BM-MSCs) 对野百合碱 (MCT) 诱导的肺动脉高压 (PAH) 大鼠模型的干预作用。方法:原代提取BM-MSCs并进行纯化、鉴定, 使用携带ACE2基因的慢病毒载体感染MSC制备ACE2-MSC, 并检测ACE2的基因与蛋白表达水平;实验动物选用健康、雄性、8周龄的SD大鼠, 随机分为正常对照组 (Control组)、MCT诱导的肺动脉高压组 (PAH组)、转导ACE2的间充质干细胞组 (ACE2-MSCs组) 以及空病毒载体的间充质干细胞组 (null-MSCs组)。于造模后第4周 (28d) 测定各组大鼠平均肺动脉压力 (mPAP) 及右心室肥厚指数 (RV/LV+S);肺组织标本作HE染色并计算肺动脉管壁厚度指数 (TI) 及面积指数 (AI);Western Blot检测肺组织中ACE2、ACE蛋白表达水平。结果:成功制备能在体外稳定过表达ACE2的ACE2-MSCs;造模后第4周 (28d), ACE2-MSCs组的mPAP、RV/LV+S、TI、AI均较PAH组及null-MSCs组有所下降 (P＜0.05), 但仍高于Control组 (P＜0.05);造模后第4周 (28d), ACE2-MSCs组肺组织中ACE2、ACE2/ACE蛋白表达水平较PAH组及null-MSCs组有所升高 (P＜0.05), 但仍低于Control组 (P＜0.05)。结论:过表达ACE2的大鼠BM-MSCs能有效降低PAH大鼠平均肺动脉压力, 改善肺血管与右心室重构, 抑制肺部炎症及调节RAS平衡。
- 间充质干细胞 /
- 血管紧张素转化酶2 /
- 肺动脉高压
Abstract: Objective: To investigate the intervention effect of rat bone marrow derived mesenchymal stem cells (BM-MSCs) overexpressing angiotensin converting enzyme 2 (ACE2) on pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) in rats.Method: BM-MSCs were infected withlentivirus vector carrying ACE2 gene in order to prepare the ACE2-MSC.Besides, the expression level of ACE2 was detected as well.Themale SD ratswere divided randomly into normal control group, MCT induced pulmonary hypertension group (PAH group), ACE2 transduction of mesenchymal stem cells group (ACE2-MSCs group) and empty vector mesenchymal stem cells group (null-MSCs group).The mean pulmonary artery pressure of rats (mPAP) and right ventricular hypertrophy index (RV/LV+S) were determined in the fourth week after the molding;The lung tissue specimens were stained with HE and the pulmonary arterial wall thicknessindex (TI) as well as area index (AI) were also calculated;The expression levels of ACE2 and ACE in lung tissue were detected by Western blotting analysis.Result: ACE2-MSCsmodelswere successfully established in vitro.The mPAP, RV/LV+S, TI, AI detected in ACE2-MSCs group in the fourth week after the modeling were lower than those in PAH group and null-MSCs group (both P＜0.05), but still higher than those in normal control group (P＜0.05).The expression levels of ACE2 and ACE2/ACE in the fourth week after the modeling in lung tissue in ACE2-MSCs group were higher than those in PAH group and null-MSCs group (both P＜0.05), but still lower than those in normal control group (P＜0.05).Conclusion: ACE2 overexpression in rat BM-MSCs can effectively reduce mPAP in PAH rats, improve pulmonary vascular remodeling and right ventricular remodeling, inhibit the inflammation in lung, and regulate the homeostasis of RAS.
- mesenchymal stem cells /
- angiotensin-converting enzyme 2 /
- pulmonary arterial hypertension

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