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贝那普利促进慢性肾脏病阶段肾病综合征患儿尿源性干细胞的增殖和分化。

Benazepril Promotes the Proliferation and Differentiation of Urine-Derived Stem Cells from Children with Nephrotic Syndrome During the Chronic Kidney Disease Stage.

作者信息

Huang Chengqiang, Yang Yuan, Li Cheng, Guo Ling, Liu Ming, Xiong Geng

机构信息

Department of Pediatric Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361101, People's Republic of China.

Sichuan Clinical Research Center for Birth Defects, Luzhou, 646000, People's Republic of China.

出版信息

Biochem Genet. 2025 Feb 19. doi: 10.1007/s10528-025-11056-9.

Abstract

Nephrotic Syndrome (NS), especially in the Chronic Kidney Disease (CKD) stage, poses significant challenges in pediatric nephrology. Urine-derived stem cells (USCs) show promise for renal repair and regeneration. While benazepril is commonly used to treat CKD, its impact on USCs from children with NS during the CKD stage is unclear. USCs were isolated from the urine of 6 healthy children and 6 with NS (CKD stage), cultured through passages, and their morphology and cell surface markers were assessed microscopically and by flow cytometry, respectively. USCs were treated with benazepril at concentrations of 1, 10, 20, 40 μmol/L, and proliferation was evaluated using the CCK-8 assay. ROS levels were measured using DCFH-DA probe, and the expression levels of IL-1β, Connexin 43, AEC, ACE2, Ang2, AQP-1 and E-cadherin were analyzed by Western Blot. Tubular epithelial cell differentiation was also examined. USCs could be cultured from both healthy and NS (CKD stage) children, but USCs from NS children only reached passage 5 and exhibited weaker proliferation and differentiation abilities compared to those from healthy children. IL-1β, Connexin 43, ROS,ACE and Ang2 levels were higher in USCs from NS children than in those from healthy children, while ACE2 showed the opposite trend. Treatment with 1 μmol/L benazepril enhanced the proliferation and differentiation ability of USCs from NS children, inhibiting the level of inflammation factors, ROS, ACE and Ang2 while promoting ACE2 expression in these cells. This study offers valuable insights for future USCs applications.

摘要

肾病综合征(NS),尤其是在慢性肾脏病(CKD)阶段,给小儿肾脏病学带来了重大挑战。尿液来源的干细胞(USCs)在肾脏修复和再生方面显示出前景。虽然苯那普利常用于治疗CKD,但其对CKD阶段NS患儿的USCs的影响尚不清楚。从6名健康儿童和6名NS(CKD阶段)儿童的尿液中分离出USCs,进行传代培养,并分别通过显微镜和流式细胞术评估其形态和细胞表面标志物。用浓度为1、10、20、40 μmol/L的苯那普利处理USCs,并使用CCK-8法评估增殖情况。使用DCFH-DA探针测量ROS水平,并通过蛋白质免疫印迹法分析IL-1β、连接蛋白43、AEC、ACE2、Ang2、AQP-1和E-钙黏蛋白的表达水平。还检查了肾小管上皮细胞分化情况。健康儿童和NS(CKD阶段)儿童的尿液均可培养出USCs,但NS儿童的USCs仅传至第5代,与健康儿童的USCs相比,其增殖和分化能力较弱。NS儿童的USCs中IL-1β、连接蛋白43、ROS、ACE和Ang2水平高于健康儿童,而ACE2则呈相反趋势。用1 μmol/L苯那普利处理可增强NS儿童USCs的增殖和分化能力,抑制炎症因子、ROS、ACE和Ang2水平,同时促进这些细胞中ACE2的表达。本研究为未来USCs的应用提供了有价值的见解。

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