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泛醇通过抑制肿瘤坏死因子-α、转化生长因子β-1、β-连环蛋白和纤连蛋白途径改善干细胞对顺铂诱导的肾损伤。

Dexpanthenol improved stem cells against cisplatin-induced kidney injury by inhibition of TNF-α, TGFβ-1, β-catenin, and fibronectin pathways.

作者信息

El-Dawy Khalifa, Barakat Nashwa, Ali Hala, Sindi Ikhlas A, Adly Heba M, Saleh Saleh A K

机构信息

Biochemistry Dept., Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.

Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

出版信息

Saudi J Biol Sci. 2023 Sep;30(9):103773. doi: 10.1016/j.sjbs.2023.103773. Epub 2023 Aug 9.

DOI:10.1016/j.sjbs.2023.103773
PMID:37635837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10450985/
Abstract

INTRODUCTION

Cisplatin interacts with DNA and induces an immunological response and reactive oxygen species, which are nephrotoxic mediators. Stem cells self-renew through symmetric divisions and can develop into other cell types due to their multipotency. Dexpanthenol has been proven to protect against renal injury.

AIM

This study aims to demonstrate that dexpanthenol could improve the effect of adipose-derived mesenchymal stem cells (ADMSC) against cisplatin-induced acute kidney injury.

METHODS

Sixty male Sprague-Dawley rats were divided into 5 groups (N = 12): control, cisplatin, cisplatin & dexpanthenol, cisplatin & ADMSC, and cisplatin & dexpanthenol & ADMSCs. On the 5th day following cisplatin injection, half the rats in each group were sacrificed, and the other half were sacrificed on the 12th day. Histopathological examination, molecular studies (IL-6, Bcl2, TGFβ-1, Caspase-3, Fibronectin, and β-catenin), antioxidants (superoxide dismutase and catalase), and renal function were all investigated.

RESULTS

In contrast to cisplatin group, the dexpanthenol and ADMSCs treatments significantly decreased renal function and oxidative stress while significantly enhancing antioxidants. Dexpanthenol improved stem cells by significantly down-regulating caspase-3, IL-6, TGF-β1, Fibronectin, and β-catenin and significantly up-regulating Bcl2 and CD34, which reversed the cisplatin effect.

CONCLUSION

Dexpanthenol enhanced ADMSCs' ability to protect against cisplatin-induced AKI by decreasing inflammation, apoptosis, and fibrosis.

摘要

引言

顺铂与DNA相互作用,诱导免疫反应和活性氧,而活性氧是肾毒性介质。干细胞通过对称分裂进行自我更新,并且由于其多能性可发育成其他细胞类型。已证实泛醇可预防肾损伤。

目的

本研究旨在证明泛醇可增强脂肪间充质干细胞(ADMSC)对顺铂诱导的急性肾损伤的作用。

方法

将60只雄性Sprague-Dawley大鼠分为5组(每组n = 12):对照组、顺铂组、顺铂+泛醇组、顺铂+ADMSC组和顺铂+泛醇+ADMSC组。在注射顺铂后的第5天,每组处死一半大鼠,另一半在第12天处死。对所有大鼠进行组织病理学检查、分子研究(白细胞介素-6、Bcl2、转化生长因子β-1、半胱天冬酶-3、纤连蛋白和β-连环蛋白)、抗氧化剂(超氧化物歧化酶和过氧化氢酶)以及肾功能检测。

结果

与顺铂组相比,泛醇和ADMSC治疗显著降低了肾功能和氧化应激,同时显著增强了抗氧化剂。泛醇通过显著下调半胱天冬酶-3、白细胞介素-6、转化生长因子-β1、纤连蛋白和β-连环蛋白,并显著上调Bcl2和CD34来改善干细胞,从而逆转了顺铂的作用。

结论

泛醇通过减少炎症、细胞凋亡和纤维化增强了ADMSC对顺铂诱导的急性肾损伤的保护能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/a77625ac99b4/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/d2ab97fea0d0/gr6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/a77625ac99b4/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/ef73ac9f793c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/87cda0d3602d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/a9212dbdd55d/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/e7835d6086ef/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/ee63e5ae94db/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/d2ab97fea0d0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/f886e9249c8f/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c29/10450985/a77625ac99b4/gr8.jpg

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