Wang Bin, Liu Ding, Zhu Qiu-Hua, Li Min, Chen Hua, Guo Ying, Fan Li-Pei, Yue Liang-Sheng, Li Liu-Yang, Zhao Ming
Department of Organ Transplantation, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Int Immunopharmacol. 2016 Jun;35:77-84. doi: 10.1016/j.intimp.2016.03.029. Epub 2016 Mar 29.
Rutin reportedly conveys many beneficial effects, including renoprotection; however, it has not yet been demonstrated to have a renoprotective effect against obstructive nephropathy. The present study is the first to show a protective effect of rutin against obstructive renal injury induced by unilateral ureteral obstruction (UUO). A total of 24 male Wistar rats were randomly divided into four groups of six rats each, including vehicle- or rutin-treated sham operated groups, and vehicle- or rutin-treated UUO groups. Rats received daily oral gavage of rutin (100mg/kg) for 2weeks. All rats were euthanized on postoperative day 14. Histological findings showed that rutin administration significantly reduced renal interstitial injury and suppressed interstitial collagen deposits in UUO rats. Moreover, rutin decreased macrophage infiltration, proinflammatory cytokine expression and phosphorylation of nuclear factor-κB p65. Furthermore, rutin inhibited extracellular matrix accumulation by reducing expression of type I/III collagen and fibronectin. Rutin also prevented the epithelial-mesenchymal transition processes of renal tubular cells by decreasing α-smooth muscle actin expression and retaining E-cadherin expression. These effects of rutin were in parallel with the reductions in Smad3 activity and pivotal to the fibrogenic potential of TGF-β1. Taken together, the renoprotective effects of rutin in obstructive nephropathy were likely due to anti-inflammatory effects and inhibition of TGF-β1/Smad3 signaling.
据报道,芦丁具有多种有益作用,包括肾脏保护作用;然而,其对梗阻性肾病的肾脏保护作用尚未得到证实。本研究首次表明芦丁对单侧输尿管梗阻(UUO)诱导的梗阻性肾损伤具有保护作用。将24只雄性Wistar大鼠随机分为四组,每组6只,包括接受载体或芦丁治疗的假手术组,以及接受载体或芦丁治疗的UUO组。大鼠连续2周每日口服灌胃芦丁(100mg/kg)。所有大鼠在术后第14天安乐死。组织学结果显示,给予芦丁可显著减轻UUO大鼠的肾间质损伤并抑制间质胶原沉积。此外,芦丁减少了巨噬细胞浸润、促炎细胞因子表达以及核因子-κB p65的磷酸化。此外,芦丁通过降低I/III型胶原和纤连蛋白的表达来抑制细胞外基质积累。芦丁还通过降低α-平滑肌肌动蛋白表达并维持E-钙黏蛋白表达来阻止肾小管细胞的上皮-间质转化过程。芦丁的这些作用与Smad3活性的降低平行,并且对TGF-β1的促纤维化潜能至关重要。综上所述,芦丁在梗阻性肾病中的肾脏保护作用可能归因于抗炎作用和对TGF-β1/Smad3信号通路的抑制。