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Mesenchymal Stromal Cell-derived Exosomes Attenuate Experimental Pulmonary Arterial Hypertension
Current Pharmaceutical Biotechnology ( IF 2.2 ) Pub Date : 2021-09-30 , DOI: 10.2174/1389201022666201231113127
LiLi Ge 1 , Wen Jiang 2 , Shanshan Zhang 3 , Jue Wang 2 , Qian Xin 2 , Chao Sun 2 , Kailin Li 2 , Tonggang Qi 2 , Yun Luan 2
Affiliation  

Background: Pulmonary arterial Hypertension (PH) is a chronic disease that ultimately progresses to right ventricular failure and death. Until now, there is still a lack of effective treatment applied. The purpose of the present study was to observe the protective effect of Mesenchymal Stromal Cell-Derived Exosomes (MSC-EXO) against experimental Pulmonary arterial Hypertension (PH) and right ventricular failure.

Methods: All the experimental rats received an intraperitoneal injection of 50 mg/kg monocrotaline to induce PH model. Three weeks after the model was successfully established, the cell Culture Media (CM) or MSC-EXO derived from human umbilical cord was administered daily via the tail vein. All animals were randomly divided into 4 groups: Control (saline-treated), MCT-PH, MCT-CM and MCT-EXO groups. Post-operation, hemodynamic data and index of right ventricular hypertrophy (RVHI) were recorded to evaluate the inhibition of MSC-EXO on MCT-induced PH. Histology, immunohistochemistry and western blot were used to analyze the effect of MSC-EXO against vascular remodeling and further reveal the mechanism.

Results: In the present study, our results showed that MSC-EXO administration could significantly reduce the Right Ventricular Systolic Pressure (RVSP) and RVHI, suppress the pulmonary vascular remodeling and The Endothelial-Mesenchymal Transition (EndMT) process.

Conclusion: Our results provided the firm information for a new method in the treatment of PH; the mechanism may be related to the inhibition of vascular remodeling and EndMT.



中文翻译:

间充质基质细胞衍生的外泌体减轻实验性肺动脉高压

背景:肺动脉高压(PH)是一种慢性疾病,最终会发展为右心室衰竭和死亡。到目前为止,仍然缺乏有效的治疗方法。本研究的目的是观察间充质基质细胞衍生的外泌体(MSC-EXO)对实验性肺动脉高压(PH)和右心室衰竭的保护作用。

方法:所有实验大鼠腹腔注射50 mg/kg野百合碱诱导PH模型。模型成功建立三周后,每天通过尾静脉给予源自人脐带的细胞培养基(CM)或MSC-EXO。所有动物随机分为 4 组:对照组(生理盐水处理)、MCT-PH、MCT-CM 和 MCT-EXO 组。术后,记录血流动力学数据和右心室肥大指数(RVHI)以评估MSC-EXO对MCT诱导的PH的抑制作用。通过组织学、免疫组化和蛋白质印迹分析MSC-EXO对血管重构的作用并进一步揭示其机制。

结果:在本研究中,我们的结果表明,MSC-EXO 给药可以显着降低右心室收缩压 (RVSP) 和 RVHI,抑制肺血管重塑和内皮-间质转化 (EndMT) 过程。

结论:我们的结果为治疗 PH 的新方法提供了可靠的信息;其机制可能与抑制血管重构和EndMT有关。

更新日期:2021-09-02
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