Renal Division, Department of Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
Biol Res. 2019 Sep 6;52(1):50. doi: 10.1186/s40659-019-0257-0.
Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO).
UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis.
The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses.
These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.
输尿管梗阻会导致肾组织损伤,并可能不可逆地进展为肾纤维化,导致肾小管细胞萎缩和凋亡。本研究旨在通过单侧输尿管梗阻(UUO)的动物模型,探讨大黄酸对肾小管细胞凋亡和肾纤维化的影响。
通过输尿管结扎诱导 UUO,然后用大黄酸或载体处理动物。对照组大鼠仅接受假手术。手术后 1 周采集肾组织,评估肾纤维化。
UUO 后,胶原 I 和α-平滑肌肌动蛋白(α-SMA)的表达以及肾小管凋亡和纤维化的严重程度均呈时间依赖性增加。大黄酸治疗部分抑制了这些反应。肾间质纤维化与 STAT3(信号转导和转录激活因子 3)磷酸化以及凋亡相关蛋白 Bax 和 Bcl2 的表达改变有关。大黄酸治疗也部分阻断了这些反应。
这些发现表明,大黄酸减轻了 UUO 模型中肾小管细胞凋亡和肾纤维化。这种治疗效果可能是通过抑制 STAT3 磷酸化介导的。