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间充质干细胞分泌的白细胞介素 10 可减轻实验性自身免疫性心肌炎。

Interleukin-10 delivered by mesenchymal stem cells attenuates experimental autoimmune myocarditis.

机构信息

Department of Newborn, Shangqiu First People's Hospital, Shangqiu 476100, Henan, China.

Department of Newborn, Shangqiu First People's Hospital, Shangqiu 476100, Henan, China.

出版信息

Int Immunopharmacol. 2020 Apr;81:106212. doi: 10.1016/j.intimp.2020.106212. Epub 2020 Feb 13.

Abstract

BACKGROUNDS

Autoimmune myocarditis is characterized by over-activated immune system attacking the cardiomyocytes, resulting in heart function decline. In the current study, we investigated the therapeutic advantages of delivering Interleukin-10 (IL-10) by mesenchymal stem cells (MSCs), both of which had immune suppression functions, in treating experimental autoimmune myocarditis.

METHODS

The mouse model of autoimmune myocarditis was established by subcutaneous injection of troponin I in A/J mice. Mouse bone marrow derived mesenchymal stem cells (BM-MSCs) with or without IL-10 overexpression, or the recombinant IL-10 protein were delivered into the mice via tail-vein injection. The inflammation and fibrosis levels of the heart were evaluated with qPCR, ELISA and histological staining. Serum level of anti-troponin-I was assessed by ELISA. Heart function analysis was conducted with echocardiography.

RESULTS

BM-MSCs overexpressing IL-10 had enhanced immune suppression functions. They also showed improved therapeutic effects from the perspective of heart function and cardiac fibrosis. The anti-troponin-I level was significantly reduced by MSCs overexpressing IL-10 when comparing with the MSCs or IL-10 protein injection.

CONCLUSION

IL-10 delivered by MSCs showed therapeutic advantages in treating experimental autoimmune myocarditis.

摘要

背景

自身免疫性心肌炎的特征是免疫系统过度激活,攻击心肌细胞,导致心功能下降。在本研究中,我们研究了间充质干细胞(MSCs)传递白细胞介素 10(IL-10)治疗实验性自身免疫性心肌炎的治疗优势,间充质干细胞本身具有免疫抑制功能。

方法

通过在 A/J 小鼠皮下注射肌钙蛋白 I 建立自身免疫性心肌炎小鼠模型。通过尾静脉注射将携带或不携带 IL-10 过表达的小鼠骨髓来源间充质干细胞(BM-MSCs)或重组 IL-10 蛋白递送至小鼠体内。通过 qPCR、ELISA 和组织学染色评估心脏的炎症和纤维化程度。通过 ELISA 评估血清抗肌钙蛋白-I 水平。通过超声心动图进行心功能分析。

结果

过表达 IL-10 的 BM-MSCs 具有增强的免疫抑制功能。从心功能和心肌纤维化的角度来看,它们也显示出更好的治疗效果。与 MSC 或 IL-10 蛋白注射相比,过表达 IL-10 的 MSC 显著降低了抗肌钙蛋白-I 水平。

结论

MSC 传递的 IL-10 在治疗实验性自身免疫性心肌炎方面显示出治疗优势。

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