人子宫内膜基质/干细胞抑制雄性Wistar大鼠顺铂诱导的急性肾损伤中的细胞凋亡。

Human Endometrial Stromal/Stem Cells Inhibit Apoptosis in Cisplatin-Induced Acute Kidney Injury in Male Wistar Rats.

作者信息

Zeinali Hadis, Azarnia Mahnaz, Keyhanvar Peyman, Moghadasali Reza, Ebrahimi-Barough Somayeh

机构信息

Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.

Faculty of Biological Sciences, Kharazmi University, Tehran, Iran. Email:

出版信息

Cell J. 2021 Oct;23(5):568-575. doi: 10.22074/cellj.2021.7322. Epub 2021 Oct 30.

DOI:10.22074/cellj.2021.7322

PMID:34837685

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8588813/

Abstract

OBJECTIVE

Acute kidney injury (AKI) is referred to as sudden decline in the function of kidney. Human endometrial stromal/stem cells (hEnSCs) are mesenchymal stem cell (MSC)-like cells, which are suitable candidates for regenerative medicine purposes, yet the effect of hEnSCs on cisplatin-induced AKI has not been studied; therefore, the present study was conducted to investigate this gap in the literature.

MATERIALS AND METHODS

In this experimental study, hEnSCs were obtained from endometrial biopsy using collagenase I and were then cultured in DMEM/F12 medium. A total of 48 male Wistar rats (150-200 g) were classified into four groups: intact -receiving no treatment, model -receiving 5 mg/kg of body weight cisplatin, as well as phosphate-buffered saline (PBS) and cell -receiving either PBS or hEnSCs for three hours after cisplatin injection, respectively. Biochemical parameters, pathologic scores, apoptosis assay, and expression were evaluated on day 5.

RESULTS

On day 5 post-transplantation we observed that HEnSCs injection has led to a decrease in both blood urea nitrogen (BUN) and serum creatinine (SCr), compared to the model and PBS groups (0.82 ± 0.03 vs. 1.42 ± 0.06, 1.09 ± 0.05 mg/dl and 61.53 ± 3.07 vs. 116.60 ± 2.12, 112.00 ± 1.35 mg/dl, respectively). The highest levels of pathologic scores were observed in model and PBS groups, while hEnSCs transplantation resulted in a decrease in pathologic scores (149.10 ± 7.03, 141.50 ± 4.68 vs. 118 ± 2.16). HEnSCs significantly decreased the percentage of TUNELpositive cells in the cell group compared with model and PBS groups (20.37 ±. 3.37 vs. 33.67 ± 1.79, 31.53 ± 1.05 in glomeruli and 15.10 ± 1.47 vs. 42.33 ± 1.72, 39.23 ± 1.61 in tubules). In addition, HEnSCs resulted in upregulation of and downregulation of in the cisplatin-induced AKI.

CONCLUSION

Our results showed that injection of hEnSCs may improve AKI through lowering the amount of apoptosis in renal cells.

摘要

目的

急性肾损伤（AKI）是指肾功能突然下降。人子宫内膜基质/干细胞（hEnSCs）是间充质干细胞（MSC）样细胞，是再生医学的合适候选细胞，但hEnSCs对顺铂诱导的AKI的影响尚未研究；因此，本研究旨在填补这一文献空白。

材料和方法

在本实验研究中，使用胶原酶I从子宫内膜活检中获取hEnSCs，然后在DMEM/F12培养基中培养。将48只雄性Wistar大鼠（150 - 200克）分为四组：完整组——不接受任何治疗，模型组——接受5毫克/千克体重的顺铂，以及磷酸盐缓冲盐水（PBS），细胞组——分别在注射顺铂后3小时接受PBS或hEnSCs。在第5天评估生化参数、病理评分、凋亡检测和表达情况。

结果

移植后第5天，我们观察到与模型组和PBS组相比，注射hEnSCs导致血尿素氮（BUN）和血清肌酐（SCr）均降低（分别为0.82±0.03对1.42±0.06，1.09±0.05毫克/分升和61.53±3.07对116.60±2.12，112.00±1.35毫克/分升）。模型组和PBS组观察到最高水平的病理评分，而hEnSCs移植导致病理评分降低（149.10±7.03，141.50±4.68对118±2.16）。与模型组和PBS组相比，hEnSCs显著降低了细胞组中TUNEL阳性细胞的百分比（肾小球中为20.37±. 3.37对33.67±1.79，31.53±1.05；肾小管中为15.10±1.47对42.33±1.72，39.23±1.61）。此外，hEnSCs导致顺铂诱导的AKI中上调和下调。