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脐带来源间充质干细胞对单侧输尿管梗阻大鼠肾纤维化的保护作用

Protective Effect of Wharton's Jelly-derived Mesenchymal Stem Cells on Renal Fibrosis in Rats with Unilateral Ureteral Obstruction.

作者信息

Kheradmand Alireza, Hashemitabar Mahmood, Kheradmand Parvin, Valizadeh Farzin, Kavosh Aryan

机构信息

Urology Department, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Anatomy and Embryology Department, Ahwaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

出版信息

Eur Urol Open Sci. 2020 Aug 17;20:48-53. doi: 10.1016/j.euros.2020.06.004. eCollection 2020 Jul.

DOI:10.1016/j.euros.2020.06.004
PMID:34337457
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8317893/
Abstract

BACKGROUND

Renal failure is a global medical problem. The use of mesenchymal stem cells (MSCs) for preservation and regeneration of renal tissue in acute and chronic kidney diseases has recently been the focus of investigation.

OBJECTIVE

To evaluate the protective effect of MSC injections in a rat model of kidney obstruction.

DESIGN SETTING AND PARTICIPANTS

We assigned 15 male Wistar rats to three separate groups: the normal group underwent left nephrectomy; the control group underwent laparotomy and left ureter ligation followed by saline injection into the aorta; and the study group received MSCs injected into the aorta inferior to the left renal artery after ligation of the left ureter. Kidneys were harvested 4 wk later and renal parenchyma samples were used for trichrome staining and for expression analyses.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

The degree of kidney fibrosis was assessed on pathology. Real-time polymerase chain reaction was used to determine expression levels of VEGF, TNF-α, and E-cadherin, and ΔCT and ΔΔCT values were calculated. Data were analyzed using SPSS v19 with paired tests and nonparametric independent-sample Kruskal-Wallis tests.

RESULTS AND LIMITATIONS

Fibrosis in the study group decreased from grade 3 or 4 to grade 1. In the control group, TNF-α expression increased and E-cadherin expression decreased. After MSC injection into obstructed kidneys, TNF-α and E-cadherin expression levels decreased and increased respectively, reaching similar levels to those in the normal group. No correlation between tissue regeneration and VEGF levels was observed. More research is needed to focus on other angiogenic factors.

CONCLUSIONS

MSC injection could prevent fibrosis in obstructed rat kidney via alterations in TNF-α and E-cadherin expression.

PATIENT SUMMARY

We investigated the effect of stem cell injection in rats with kidney obstruction. The treatment led to changes in the levels of two biomarkers and reduced the amount of kidney fibrosis caused by kidney obstruction.

摘要

背景

肾衰竭是一个全球性的医学问题。近年来,间充质干细胞(MSCs)在急性和慢性肾脏疾病中用于肾脏组织的保存和再生已成为研究热点。

目的

评估间充质干细胞注射对大鼠肾梗阻模型的保护作用。

设计、场所和参与者:我们将15只雄性Wistar大鼠分为三组:正常组行左肾切除术;对照组行剖腹术及左输尿管结扎,随后经主动脉注射生理盐水;研究组在左输尿管结扎后经主动脉向左肾动脉下方注射间充质干细胞。4周后取出肾脏,肾实质样本用于三色染色和表达分析。

结果测量和统计分析

通过病理学评估肾脏纤维化程度。采用实时聚合酶链反应测定血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)和E-钙黏蛋白的表达水平,并计算ΔCT和ΔΔCT值。使用SPSS v19软件进行数据分析,采用配对检验和非参数独立样本Kruskal-Wallis检验。

结果与局限性

研究组纤维化程度从3级或4级降至1级。对照组中,TNF-α表达增加,E-钙黏蛋白表达减少。向梗阻肾脏注射间充质干细胞后,TNF-α和E-钙黏蛋白表达水平分别降低和升高,达到与正常组相似的水平。未观察到组织再生与VEGF水平之间的相关性。需要更多研究关注其他血管生成因子。

结论

间充质干细胞注射可通过改变TNF-α和E-钙黏蛋白的表达来预防大鼠梗阻性肾脏的纤维化。

患者总结

我们研究了干细胞注射对大鼠肾梗阻的影响。该治疗导致两种生物标志物水平发生变化,并减少了肾梗阻引起的肾脏纤维化量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6688/8317893/99fc54228415/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6688/8317893/c59d6da8d091/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6688/8317893/648110f8c755/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6688/8317893/99fc54228415/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6688/8317893/c59d6da8d091/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6688/8317893/648110f8c755/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6688/8317893/99fc54228415/gr3.jpg

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