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透明质酸修饰的骨髓间充质干细胞通过抑制Wnt/β-连环蛋白信号通路对阿霉素诱导的肾纤维化的肾保护作用

Renoprotective effect of bone marrow mesenchymal stem cells with hyaluronic acid against adriamycin- induced kidney fibrosis via inhibition of Wnt/β-catenin pathway.

作者信息

Serag Waleed M, Barakat Nashwa, Elshehabi Mohammed E, Hafez Hani S, Zahran Faten

机构信息

Chemistry Department, Faculty of Science, Suez University, Suez, Egypt.

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

出版信息

Int J Biol Macromol. 2022 May 15;207:741-749. doi: 10.1016/j.ijbiomac.2022.03.156. Epub 2022 Mar 27.

Abstract

AIM

The current study aimed to explore the pretreatment of bone marrow mesenchymal stem cells (BMSCs) with hyaluronic acid (HA) on renal fibrosis in Adriamycin- induced CKD in rats.

MATERIAL AND METHODS

Sixty male SD rats were alienated into 4 equal groups; The control group: rats received two saline injections at 1 and 14 days, adriamycin (ADR) group: rats were injected i.v. twice via tail vein at day one and after 2 weeks, BMSCs group; rats were injected i.v. twice after 5 days of each ADR injection, and HA+BMSCs; rats were i.v. injected twice with BMSCs pretreated with 1 mg/ml HA after 5 days of each ADR injection. Protective role of BMSCs on renal function and morphology was detected using biochemical analysis, molecular studies, histopathological, and immunohistohemical investigations.

RESULTS

Pretreatment of BMSCs with HA showed significant decrease in KIM-1, and increase in serum albumin compared to CKD group (p <0.05). Moreover, it reduced the expression of the apoptotic marker Caspase-3, the inflammatory markers TNF and IL-6, and the fibrotic markers Wnt7a, β-catenin, and fibronectin1 than the CKD group (p < 0.05).

CONCLUSION

The current outcomes suggested that BMSCs preconditioned with HA could attenuate the renal fibrosis in adriamycin- induced CKD.

摘要

目的

本研究旨在探讨透明质酸(HA)预处理骨髓间充质干细胞(BMSCs)对阿霉素诱导的大鼠慢性肾脏病(CKD)肾纤维化的影响。

材料与方法

将60只雄性SD大鼠分为4组,每组15只;对照组:大鼠在第1天和第14天接受两次生理盐水注射;阿霉素(ADR)组:大鼠在第1天和2周后经尾静脉注射阿霉素2次;BMSCs组:每次阿霉素注射5天后经尾静脉注射BMSCs 2次;HA+BMSCs组:每次阿霉素注射5天后经尾静脉注射用1mg/ml HA预处理的BMSCs 2次。采用生化分析、分子研究、组织病理学和免疫组化研究检测BMSCs对肾功能和形态的保护作用。

结果

与CKD组相比,HA预处理的BMSCs组KIM-1显著降低,血清白蛋白升高(p<0.05)。此外,与CKD组相比,其凋亡标志物Caspase-3、炎症标志物TNF和IL-6以及纤维化标志物Wnt7a、β-连环蛋白和纤连蛋白1的表达均降低(p<0.05)。

结论

目前的研究结果表明,HA预处理的BMSCs可减轻阿霉素诱导的CKD大鼠的肾纤维化。

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