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深入了解人牙髓干细胞及其分泌组在顺铂诱导的肾毒性中的保护能力:对氧化应激和组织学变化的影响。

Insights into the protective capacity of human dental pulp stem cells and its secretome in cisplatin-induced nephrotoxicity: effects on oxidative stress and histological changes.

作者信息

Ranjbar Esmail, Tavakol Afshari Jalil, KhajaviRad Abolfazl, Ebrahimzadeh-Bideskan Alireza, Shafieian Reyhaneh

机构信息

Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Basic Clin Physiol Pharmacol. 2022 Oct 10;34(3):349-356. doi: 10.1515/jbcpp-2022-0159. eCollection 2023 May 1.

Abstract

OBJECTIVES

Acute renal injury (AKI) is a major limiting factor for cisplatin administration. Recent evidence suggests the potential contribution of mesenchymal stem cells (MSCs) to rehabilitation from several disorders via both direct and indirect routes. Thus, the present study aimed, for the first time, to explore and compare the reno-protective potential of human dental pulp-derived stem cells (hDPSCs) vs. hDPSC-conditioned medium (hDPSC-CM) in recovery of impaired kidney tissues in a rat animal model of cisplatin-induced AKI.

METHODS

AKI was induced via cisplatin injection (n=36). One day after, 24 rats were treated with either hDPSCs or hDPSC-CM (n=12). An extra set of rats (n=12) served as sham group. On days 2 or 7 (n=6), rats were humanly sacrificed for further analysis. Renal injury was explored via measuring serum creatinine and BUN. Renal level of oxidative stress was assessed by determining malondialdehyde, and enzymatic activities of superoxide dismutase and catalase. Renal histopathological changes were scored for comparison among different experimental groups.

RESULTS

A single dose of cisplatin resulted in considerable renal dysfunction and oxidative stress. Treatment with hDPSCs or hDPSC-CM resulted in significantly restored renal function, reduced level of oxidative stress, and improved histopathological manifestations. Furthermore, as compared to hDPSC-CM, administration of hDPSCs led to superior results in AKI-induced animals.

CONCLUSIONS

The current study described the first comparative evidence of reno-protective potential of hDPSCs and their CM against cisplatin-induced nephrotoxicity in an AKI rat model, proposing them as useful adjunctive therapy in AKI. Yet, future explorations are still needed.

摘要

目的

急性肾损伤(AKI)是顺铂给药的主要限制因素。最近的证据表明,间充质干细胞(MSCs)通过直接和间接途径对多种疾病的康复具有潜在贡献。因此,本研究首次旨在探索和比较人牙髓来源干细胞(hDPSCs)与人牙髓干细胞条件培养基(hDPSC-CM)在顺铂诱导的AKI大鼠动物模型中受损肾组织恢复方面的肾保护潜力。

方法

通过注射顺铂诱导AKI(n = 36)。一天后,24只大鼠接受hDPSCs或hDPSC-CM治疗(n = 12)。另一组大鼠(n = 12)作为假手术组。在第2天或第7天(n = 6),对大鼠实施安乐死以进行进一步分析。通过测量血清肌酐和血尿素氮来探究肾损伤。通过测定丙二醛以及超氧化物歧化酶和过氧化氢酶的酶活性来评估肾脏氧化应激水平。对肾脏组织病理学变化进行评分,以比较不同实验组之间的差异。

结果

单剂量顺铂导致明显的肾功能障碍和氧化应激。用hDPSCs或hDPSC-CM治疗可显著恢复肾功能,降低氧化应激水平,并改善组织病理学表现。此外,与hDPSC-CM相比,给予hDPSCs在AKI诱导的动物中产生了更好的结果。

结论

本研究首次描述了hDPSCs及其条件培养基在AKI大鼠模型中对顺铂诱导的肾毒性的肾保护潜力的比较证据,提出它们可作为AKI的有用辅助治疗方法。然而,仍需要进一步探索。

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