5-Aza诱导BM-MSCs移植对大鼠心肌梗死面积、相关细胞因子及钾离子通道蛋白的影响

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (1): 20-26.

5-Aza诱导BM-MSCs移植对大鼠心肌梗死面积、相关细胞因子及钾离子通道蛋白的影响

李明阳¹, 王淑霞¹, 赵静苗², 王秋萍², 陈凭⁴, 金华², 胡继宏^3*

甘肃中医药大学 1.公共卫生学院; 2.基础医学院; 3.科研实验中心,甘肃兰州 730000;
4.兰州市第二人民医院体检中心, 甘肃兰州 730000

收稿日期:2020-01-02 修回日期:2020-04-28 出版日期:2021-01-05 发布日期:2020-12-30
通讯作者: ^*hujihonghappy@163.com
基金资助:
国家自然科学基金 (81260597)

Effects of 5-Aza-induced BM-MSCs transplantation on myocardial infarction area, related cytokines and potassium ion channels in rats

LI Ming-yang¹, WANG Shu-xia¹, ZHAO Jing-miao², WANG Qiu-ping², CHEN Ping⁴, JIN Hua², HU Ji-hong^3*

1. College of Public Health; 2. Basic Medical College;3. Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou 730000;
4. Physical Examination Center,the Second People's Hospital of Lanzhou, Lanzhou 730000, China

Received:2020-01-02 Revised:2020-04-28 Online:2021-01-05 Published:2020-12-30
Contact: ^*hujihonghappy@163.com

摘要/Abstract

摘要： 目的观察5-氮杂胞苷(5-Aza)诱导骨髓间充质干细胞(BM-MSCs)移植对大鼠心肌梗死面积、相关细胞因子及钾离子通道蛋白表达的影响。方法大鼠随机分为对照组、模型组、阴性对照组(细胞培养液)、BM-MSCs组和5-Aza-BM-MSCs组。冠状动脉结扎建立心肌梗死模型,采用4点注射法进行细胞移植。HE染色观察梗死心肌组织病理,免疫组化检测梗死区caspase-3、beclin-2、VEGF、PGI₂、超氧化物歧化酶(SOD)、IL-3、IL-6和TNF-α的表达;Western blot检测钾离子通道Kv1.2和Kv1.5蛋白的表达。结果 1)与对照组相比,模型组心肌梗死面积明显增大,caspase-3、beclin-2、VEFG、PGI₂、IL-3、IL-6和TNF-α表达水平提高(P＜0.05);SOD、Kv1.2和Kv1.5表达水平降低(P＜0.05); 2)与模型组相比,BM-MSCs组和5-Aza-BM-MSCs组心肌梗死面积明显减小,caspase-3、beclin-2、IL-3、IL-6和TNF-α表达水平降低(P＜0.05),Kv1.5、VEGF、PGI₂、和SOD表达水平提高(P＜0.05),Kv1.2 BM-MSCs组表达降低而5-Aza-BM-MSCs组表达提高(P＜0.05);3)与BM-MSCs组比较,5-Aza-BM-MSCs组心肌梗死面积减小,caspase-3、和IL-6表达水平降低(P＜0.05),Kv1.2、VEGF和SOD表达水平均提高(P＜0.05)。结论 5-Aza-BM-MSCs可以更有效的减少炎性反应与细胞凋亡,促进新生血管生成,提高心肌抗氧化能力,减少心肌梗死面积,促进钾离子通道蛋白Kv1.2的表达。

关键词: 骨髓间充质干细胞, 5-氮杂胞苷, 心肌梗死, 钾离子通道

Abstract: Objective To observe the effects of 5-azacytidine(5-Aza)-induced bone marrow mesenchymal stem cells(BM-MSCs) transplantation on the myocardial infarction area, the expression of related cytokines and potassium channels in rats. Methods Rats were randomly divided into control group, model group, blank control group, BM-MSCs group and 5-Aza-BM-MSCs group. Coronary artery ligation was used to develope a model of myocardial infarction, and cell transplantation was performed using a 4-point injection method. HE staining was used to observe the pathology of infarct myocardium, and the expression of caspase-3, beclin-2, VEGF, PGI₂, superoxide dismutase (SOD), IL-3, IL-6 and TNF-α in infarct areas were detected by immunohistochemistry. The Kv1.2 and Kv1.5 proteins expressions of potassium channels were detected by Western blot. Results 1)Compared with the control group, the area of myocardial infarction and the expression level of caspase-3, beclin-2, VEFG, PGI₂, IL-3, IL-6 and TNF-α in the model group all significantly increased (P＜0.05). However, the expression level of Kv1.2 and Kv1.5 were reduced (P＜0.05). 2)Compared with the model group, the area of myocardial infarction and caspase-3, beclin-2, and IL-3, IL-6 and TNF-α expression level significantly reduced both in the BM-MSCs group and the 5-Aza-BM-MSCs group (P＜0.05), Kv1.5, VEGF, PGI₂, and SOD expression level increased(P＜0.05); Kv1.2 in BM-MSCs group decreased, but increased in 5-Aza-BM-MSCs group (P＜0.05). 3)Compared with the BM-MSCs group, the area of myocardial infarction and the expression of caspase-3 and IL-6 decreased in the 5-Aza-BM-MSCs group (P＜0.05), Kv1.2, VEGF and SOD expression level increased (P＜0.05). Conclusions 5-Aza-BM-MSCs more effectively reduces inflammatory response and apoptosis, promotes neovascularization, improves myocardial antioxidant capacity, reduces myocardial infarction area, and promotes the expression of potassium ion channel Kv1.2 protein as compare to single BM-MSCs transplantation.

Key words: bone marrow mesenchymal stem cells, 5-azacytidine, myocardial infarction, potassium ion channel

中图分类号:

R394.2
Q253

李明阳, 王淑霞, 赵静苗, 王秋萍, 陈凭, 金华, 胡继宏. 5-Aza诱导BM-MSCs移植对大鼠心肌梗死面积、相关细胞因子及钾离子通道蛋白的影响[J]. 基础医学与临床, 2021, 41(1): 20-26.

LI Ming-yang, WANG Shu-xia, ZHAO Jing-miao, WANG Qiu-ping, CHEN Ping, JIN Hua, HU Ji-hong. Effects of 5-Aza-induced BM-MSCs transplantation on myocardial infarction area, related cytokines and potassium ion channels in rats[J]. Basic & Clinical Medicine, 2021, 41(1): 20-26.

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