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人羊膜间充质干细胞通过抑制炎症和调节炎症性丝裂原活化蛋白激酶/核因子κB信号通路,对异丙肾上腺素(ISO)诱导的心肌损伤发挥心脏保护作用。

Human amniotic membrane mesenchymal stem cells exert cardioprotective effects against isoproterenol (ISO)-induced myocardial injury through suppression of inflammation and modulation of inflammatory MAPK/NF-κB pathway.

作者信息

Naseroleslami Maryam, Aboutaleb Nahid

机构信息

Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Cell Tissue Bank. 2022 Mar;23(1):67-77. doi: 10.1007/s10561-021-09915-x. Epub 2021 Mar 17.

DOI:10.1007/s10561-021-09915-x
PMID:33733423
Abstract

A common cause of mortality around the world is ischemic myocardial injury. The study was conducted to examine the ability of amniotic membrane mesenchymal stem cells (AMSCs) for protection against isoproterenol (ISO)-induced myocardial injury and attempted to show the possible mechanisms by which AMSCs that can be linked to inhibition of inflammation by targeting inflammatory MAPK/NF-κB pathway. Model was established by subcutaneous injection of 170 mg/kg/day of ISO for four consecutive days. Flow cytometry and echocardiography were carried out to evaluate characterization of hAMSCs and cardiac function, respectively. The expression of inflammatory cytokines was determined using ELISA assay. The activities of NF-κB and phosphorylated p38 MAPK were measured using immunohistochemical assessments. The results showed that ISO administration was resulted in cardiac dysfunction, increased levels of inflammatory cytokines that reversed by intramyocardially administration of AMSCs (P < 0. 05). Cardioprotective effects of AMSCs were associated with a significant decreased expression of NF-κB and reduced levels of phosphorylated p38 MAPK (P < 0. 05). In conclusion, our finding showed that intramyocardially administration of AMSCs could contribute to improvement of heart function and inhibition of inflammation in the site of injury by targeting inflammatory MAPK/NF-κB pathway.

摘要

全球范围内,缺血性心肌损伤是导致死亡的常见原因。本研究旨在考察羊膜间充质干细胞(AMSCs)对异丙肾上腺素(ISO)诱导的心肌损伤的保护能力,并试图揭示AMSCs可能通过靶向炎性丝裂原活化蛋白激酶/核因子κB(MAPK/NF-κB)信号通路抑制炎症反应的机制。通过连续4天皮下注射170mg/kg/天的ISO建立模型。分别采用流式细胞术和超声心动图评估人羊膜间充质干细胞(hAMSCs)的特性和心脏功能。采用酶联免疫吸附测定法(ELISA)检测炎性细胞因子的表达。采用免疫组织化学评估法检测NF-κB和磷酸化p38 MAPK的活性。结果显示,给予ISO可导致心脏功能障碍,炎性细胞因子水平升高,而心肌内注射AMSCs可逆转这种情况(P<0.05)。AMSCs的心脏保护作用与NF-κB表达显著降低及磷酸化p38 MAPK水平降低有关(P<0.05)。总之,我们的研究结果表明,心肌内注射AMSCs可通过靶向炎性MAPK/NF-κB信号通路改善心脏功能并抑制损伤部位的炎症反应。

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