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参与胚胎干细胞移植治疗的钙敏感受体通过抑制大鼠细胞凋亡和氧化应激来减轻急性心肌梗死。

Calcium sensing receptor involving in therapy of embryonic stem cell transplantation alleviates acute myocardial infarction by inhibiting apoptosis and oxidative stress in rats.

作者信息

Yuan Hui, Yang Guohong, Li Shu, Li Li, Wei Tao, Song Gaochen, Luan Hairong, Meng Jin, Wang Qi, Yu Yaquan, Sun Jian

机构信息

Mudanjiang Medical University, Mudanjiang, 157011, China.

出版信息

Iran J Basic Med Sci. 2020 Oct;23(10):1353-1359. doi: 10.22038/ijbms.2020.47436.10916.

Abstract

OBJECTIVES

The aims of the present study were to investigate the expression of calcium sensing receptor (CaSR) at different times in acute myocardial infarction (AMI) rat myocardial tissue after mouse embryonic stem cells (mESCs) transplantation treatment and to assess its effects on apoptosis and oxidative stress of cardiomyocytes.

MATERIALS AND METHODS

The AMI rats were treated with mESCs, Calindol (a CaSR agonist) and Calhex231 (a CaSR inhibitor). Serum measurements, Echocardiographic analysis and TUNEL assay were performed. Myocardial ultrastructure changes were viewed by electron microscopy. Additionally, western blotting was used to detect the protein expressions.

RESULTS

Compared to the sham group, it was found that the expression levels of CaSR, caspase-3, cytoplasmic cytochrome C (cyt-C) and Bcl2-associated x (Bax), and the levels of Malondialdehyde (MDA) were significantly increased in both AMI and AMI + mESCs + Calindol groups with the development of myocardial infarction. Furthermore, the ultra-microstructure of cardiomyocyte was highly damaged, the expression levels of mitochondrial cyt-C and B-cell lymphoma 2 (Bcl-2) were significantly decreased, and there was decreased activity of superoxide dismutase (SOD). However, the combination of Calhex231 and mESCs transplantation could inhibit these changes.

CONCLUSION

Our results suggested that CaSR expression in myocardial tissue of AMI rats was increased over time, and that Calhex231 could enhance the efficacy of ESCs transplantation for the treatment of AMI, which would be a new therapeutic strategy for the treatment of AMI.

摘要

目的

本研究旨在探讨小鼠胚胎干细胞(mESCs)移植治疗后急性心肌梗死(AMI)大鼠心肌组织中钙敏感受体(CaSR)在不同时间的表达情况,并评估其对心肌细胞凋亡和氧化应激的影响。

材料与方法

对AMI大鼠进行mESCs、卡林多(一种CaSR激动剂)和卡赫克斯231(一种CaSR抑制剂)治疗。进行血清检测、超声心动图分析和TUNEL检测。通过电子显微镜观察心肌超微结构变化。此外,采用蛋白质印迹法检测蛋白质表达。

结果

与假手术组相比,发现随着心肌梗死的发展,AMI组和AMI + mESCs + 卡林多组中CaSR、半胱天冬酶-3、细胞质细胞色素C(cyt-C)和Bcl2相关X蛋白(Bax)的表达水平以及丙二醛(MDA)水平均显著升高。此外,心肌细胞超微结构严重受损,线粒体cyt-C和B细胞淋巴瘤2(Bcl-2)的表达水平显著降低,超氧化物歧化酶(SOD)活性下降。然而,卡赫克斯231与mESCs移植联合应用可抑制这些变化。

结论

我们的结果表明,AMI大鼠心肌组织中CaSR表达随时间增加,卡赫克斯231可增强ESCs移植治疗AMI的疗效,这将是治疗AMI的一种新的治疗策略。

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