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研究利用新型支架(PGS-co-PCL/PGC/PPy/Gelatin)在雄性 Wistar 大鼠心肌缺血再灌注诱导的肾衰中对 hAMSCs 的间接治疗效果。

Investigating the indirect therapeutic effect of hAMSCs utilizing a novel scaffold (PGS-co-PCL/PGC/PPy/Gelatin) in myocardial ischemia-reperfusion-induced renal failure in male Wistar rats.

机构信息

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

Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

出版信息

Tissue Cell. 2024 Aug;89:102428. doi: 10.1016/j.tice.2024.102428. Epub 2024 Jun 1.

Abstract

BACKGROUND

Myocardial ischemia-reperfusion (MI/R) occurs due to temporary or permanent interruptions in the coronary and circulatory system, indirectly affecting kidney function through reduced cardiac output for metabolic needs. In this study, the aim was to explore the indirect effects of using human amniotic membrane mesenchymal stem cells (hAMSCs) with the PGS-co-PCL/PGC/PPy/Gelatin scaffold in male rats with renal failure induced by miocardial ischemia-reperfusion.

METHODS

MI/R injury was induced in 48 male Wistar rats through left anterior descending artery ligation, divided into four groups (n=12); control group, cell group, scaffold group, and celss+scaffold group. Evaluations were conducted at two and thirty days post MI/R injury, encompassing echocardiography, biochemical, inflammatory markers analysis, and histological assessment.

RESULTS

Echocardiographic findings exhibited notable enhancement in ejection fraction, fractional shortening, and stroke volume of treated groups compared to controls after 30 days (P< 0.05). Serum creatinine (P< 0.001) and urea (P< 0.05) levels significantly decreased in the scaffold+cells group) compared to the control group. The treated cells+ scaffold group displayed improved kidney structure, evidenced by larger glomeruli and reduced Bowman's space compared to the control group (P< 0.01). Immunohistochemical analysis indicated reduced TNF-α protein in the scaffold+ cells group (P< 0.05) in contrast to the control group (P< 0.05). Inflammatory factors IL-6, TNF-α, and AKT gene expression in renal tissues were improved in scaffold+ cells-treated animals.

CONCLUSION

Our research proposes the combination of hAMSCs and the PGS-co-PCL/PGC/PPy/Gelatin scaffold in MI/R injured rats appears to enhance renal function and reduce kidney inflammation by improving cardiac output.

摘要

背景

心肌缺血再灌注(MI/R)是由于冠状动脉和循环系统的暂时或永久性中断引起的,通过减少代谢需求的心脏输出间接影响肾脏功能。在这项研究中,目的是探讨在由心肌缺血再灌注引起的肾功能衰竭的雄性大鼠中使用人羊膜间充质干细胞(hAMSCs)与 PGS-co-PCL/PGC/PPy/明胶支架的间接作用。

方法

通过左前降支结扎在 48 只雄性 Wistar 大鼠中诱导 MI/R 损伤,分为四组(n=12);对照组、细胞组、支架组和细胞+支架组。在 MI/R 损伤后 2 天和 30 天进行评估,包括超声心动图、生化、炎症标志物分析和组织学评估。

结果

超声心动图结果显示,与对照组相比,治疗组在 30 天后射血分数、分数缩短和每搏量明显提高(P<0.05)。与对照组相比,血清肌酐(P<0.001)和尿素(P<0.05)水平在支架+细胞组显著降低。与对照组相比,治疗细胞+支架组的肾脏结构得到改善,表现为肾小球增大和Bowman 空间减少(P<0.01)。免疫组化分析表明,与对照组相比,支架+细胞组 TNF-α 蛋白减少(P<0.05)。支架+细胞处理动物的肾组织中炎症因子 IL-6、TNF-α 和 AKT 基因表达得到改善。

结论

我们的研究提出了在 MI/R 损伤大鼠中联合使用 hAMSCs 和 PGS-co-PCL/PGC/PPy/明胶支架,通过改善心输出量来增强肾功能和减轻肾脏炎症。

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