Preventive Medicine Ward, Wei Hai Municpal Hospital, Shandong University, Weihai 2642, Shandong, China.
Intensive Care Unit(ICU), Wei Hai Municpal Hospital, Shandong University, Weihai 264200, Shandong, China.
Int Immunopharmacol. 2020 Nov;88:106719. doi: 10.1016/j.intimp.2020.106719. Epub 2020 Sep 8.
Myocardial ischemia-reperfusion injury (MI-RI) has many adverse complications with high mortality rate. In the current study, we investigated the therapeutic advantages of delivering Interleukin-37 (IL-37) by induced cardiospheres (iCS), generated from adult skin fibroblasts via somatic reprogramming, in treating the mice model MI-RI.
The mouse model of MI-RI was established and the iCS cells with IL-37 overexpression (iCS-IL37) were transplanted into the mice via tail-vein injection. Left ventricular (LV) dimensions and LV pressure-volume measurements were assessed by parasternal long-axis echocardiography and hemodynamic assessment. The infarct size was determined by histology analysis. And the inflammatory responses were analyzed by using enzyme-linked immunosorbent assay (ELISA).
The LV function was significantly improved after the iCS-IL37 transplantation when compared to the vehicle control group and iCS group, including the end-systolic pressure and dP/dtMax. Furthermore, the infarct size was significantly decreased after the iCS-IL37 transplantation. The protein levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were down-regulated by the iCS-IL37 transplantation.
The present study indicated that the iCS with IL-37 overexpression had therapeutic effects on the mice model of MI-RI.
心肌缺血再灌注损伤(MI-RI)有许多不良并发症,死亡率很高。在本研究中,我们通过诱导心肌球体(iCS)来研究白细胞介素-37(IL-37)的治疗优势,iCS 是通过体细胞核移植技术从成人皮肤成纤维细胞生成的。
建立了 MI-RI 小鼠模型,并通过尾静脉注射将过表达 IL-37 的 iCS 细胞(iCS-IL37)移植到小鼠体内。通过胸骨旁长轴超声心动图和血流动力学评估评估左心室(LV)尺寸和 LV 压力-容积测量。通过组织学分析确定梗死面积。通过酶联免疫吸附试验(ELISA)分析炎症反应。
与载体对照组和 iCS 组相比,iCS-IL37 移植后 LV 功能明显改善,包括收缩末期压力和 dP/dtMax。此外,iCS-IL37 移植后梗死面积明显减小。iCS-IL37 移植后促炎细胞因子(包括肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β))的蛋白水平下调。
本研究表明,过表达 IL-37 的 iCS 对 MI-RI 小鼠模型具有治疗作用。