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诱导心肌球通过分泌白细胞介素 10 对心肌缺血再灌注损伤的保护作用。

Protective effects of induced cardiosphere on myocardial ischemia-reperfusion injury through secreting interleukin 10.

机构信息

Department of Cardiology, Qingdao Municipal Hospital, Qingdao 266000, Shandong, China.

Department of Cardiology, Affiliated Hospital of Hebei University, Baoding 071000, Hebei, China.

出版信息

Int Immunopharmacol. 2020 Mar;80:106207. doi: 10.1016/j.intimp.2020.106207. Epub 2020 Jan 17.

Abstract

BACKGROUNDS

Myocardial ischemia-reperfusion injury (MI-RI) has many adverse complications with high mortality rate. It has been demonstrated that the induced cardiospheres (iCS), generated from adult skin fibroblasts via somatic reprogramming, represents a novel source for cell therapy in myocardial infarction. However, whether the iCS could also be applied to treat MI-RI remains unclear. Thus, we investigated the therapeutic application of iCS in the mice model MI-RI.

METHODS

The mice model of MI-RI was established and the iCS cells were transplanted to the mice via tail-vein injection. Left ventricular (LV) dimensions and LV pressure-volume measurements were assessed by parasternal long-axis echocardiography. The infarct size was determined by histology analysis. And the inflammatory responses were analyzed by using enzyme-linked immunosorbent assay (ELISA).

RESULTS

The LV function was significantly improved after the iCS transplantation when compared to the vehicle control group, including the end-systolic pressure and dP/dtMax. Furthermore, the infarct size was significantly decreased after the iCS 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 transplantation while the IL-10 was up-regulated. The anti-inflammatory factor IL-10 was found to be expressed and secreted by the iCS cells and knocking down the IL-10 in iCS would significantly impair the therapeutic effects of iCS in the mice model of MI-RI.

CONCLUSION

The present study indicated that the iCS had therapeutic effects on the mice model of MI-RI through secreting the IL-10.

摘要

背景

心肌缺血再灌注损伤(MI-RI)具有许多不良并发症,死亡率很高。已经证明,通过体细胞核移植技术从成人皮肤成纤维细胞诱导产生的心肌球体(iCS)是心肌梗死细胞治疗的一种新来源。然而,iCS 是否也可用于治疗 MI-RI 尚不清楚。因此,我们研究了 iCS 在 MI-RI 小鼠模型中的治疗应用。

方法

建立 MI-RI 小鼠模型,并通过尾静脉注射将 iCS 细胞移植到小鼠体内。通过胸骨旁长轴超声心动图评估左心室(LV)尺寸和 LV 压力-容积测量。通过组织学分析确定梗死面积。并通过酶联免疫吸附试验(ELISA)分析炎症反应。

结果

与载体对照组相比,iCS 移植后 LV 功能明显改善,包括收缩末期压力和 dP/dtMax。此外,iCS 移植后梗死面积明显减小。iCS 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,而白细胞介素-10(IL-10)上调。发现 iCS 细胞表达和分泌抗炎因子 IL-10,敲低 iCS 中的 IL-10 会显著损害 iCS 在 MI-RI 小鼠模型中的治疗效果。

结论

本研究表明,iCS 通过分泌 IL-10 对 MI-RI 小鼠模型具有治疗作用。

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