Siregar Safendra, Noegroho Bambang Sasongko, Karim Muhammad Ilhamul
Department of Urology, Faculty of Medicine Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital, Indonesia.
Turk J Urol. 2020 May 1;46(3):236-242. doi: 10.5152/tud.2020.20024. Print 2020 May.
The fibrotic process of kidney resulting in glomerulosclerosis was found in patients with ureteropelvic junction obstruction (UPJO) who underwent renal biopsy during pyeloplasty. Transforming growth factor β1 (TGF-β1) plays a role in collagen accumulation, resulting in fibrosis. Adipose tissue-derived stem cells (ADSCs) have an anti-apoptotic effect on target cells and enhance the kidney function recovery. We will further investigate the use of ADSC in the prevention of kidney fibrosis in the unilateral UPJO model of Wistar rats.
A total of twenty-two 12-week-old Wistar rats were divided into three groups. We made the UPJO models using nylon 6-0 inside the left ureter and tied the ureter with nylon 6-0, creating partial ureteral obstruction. The treatment group was then injected with 1.0 × 10 cells of human ADSC via the tail vein of rats. All rats were euthanized after 2 and 4 weeks of treatment. The left kidney used hematoxylin-eosin for histopathological examination. Statistical analysis using one-way analysis of variance (ANOVA) was done with SPSS version 21.0.
TGF-β1 concentration in the treatment group was significantly lower in the 4 week of observation (p4=0.0001), as well as collagen type 1, which was also significantly lower in the 4 week (p4=0.0001). There was a significant difference in the glomerulus count between the control group and the human ADSC (hADSC) group therapy in week 2 and week 4 (p2=0.0001 and p4=0.026).
Administration of hADSC therapy reduces TGF-β1 and collagen type 1 levels and then improves the histopathological features in the process of renal fibrosis in the UPJO model.
在肾盂成形术期间接受肾活检的输尿管肾盂连接部梗阻(UPJO)患者中发现了导致肾小球硬化的肾脏纤维化过程。转化生长因子β1(TGF-β1)在胶原蛋白积累中起作用,导致纤维化。脂肪组织来源的干细胞(ADSCs)对靶细胞具有抗凋亡作用,并能促进肾功能恢复。我们将进一步研究ADSC在Wistar大鼠单侧UPJO模型中预防肾纤维化的应用。
将22只12周龄的Wistar大鼠分为三组。我们在左输尿管内使用尼龙6-0制作UPJO模型,并用尼龙6-0结扎输尿管,造成部分输尿管梗阻。然后通过大鼠尾静脉向治疗组注射1.0×10个人类ADSC细胞。治疗2周和4周后对所有大鼠实施安乐死。取左肾用苏木精-伊红染色进行组织病理学检查。使用SPSS 21.0版本进行单因素方差分析(ANOVA)统计分析。
治疗组在观察第4周时TGF-β1浓度显著降低(p4 = 0.0001),I型胶原蛋白在第4周时也显著降低(p4 = 0.0001)。对照组与人类ADSC(hADSC)组治疗在第2周和第4周时肾小球计数存在显著差异(p2 = 0.0001和p4 = 0.026)。
给予hADSC治疗可降低TGF-β1和I型胶原蛋白水平,进而改善UPJO模型肾纤维化过程中的组织病理学特征。