Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Neurogenic Inflammation Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmacol Rep. 2017 Aug;69(4):648-657. doi: 10.1016/j.pharep.2017.03.002. Epub 2017 Mar 14.
It is well established that renin-angiotensin system (RAS) play a central role in pathophysiology of renal damage following unilateral ureteral obstruction (UUO). The present study investigated the effects of thymoquinone and RAS blockade on renal tissue damage and renal expression of angiotensin II after UUO in rats.
Forty male rats were divided to five groups: Sham-operated group, UUO group and rats with UUO treated with losartan, captopril and thymoquinone. The rats were evaluated two weeks after UUO by measuring renal oxidative stress, apoptosis and the expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP-1) and angiotensin II.
Two weeks after UUO there was a significant increase in the number of renal apoptotic cells and renal malondialdehyde and TNF-α expression. In addition, renal total thiol content and the activity of antioxidant enzymes were significantly decreased in UUO group, compared with the sham group. Also, UUO was associated with upregulation in the expression of angiotensin II and MCP-1 in the obstructed kidney. Losartan, captopril and thymoquinone significantly improved oxidative damage, apoptosis and TNF-α expression and markedly decreased the upregulation of angiotensin II and MCP-1 compared with the UUO group.
The current study suggests that thymoquinone is able to improve the UUO-induced renal tissue damage. These favorable actions of thymoquinone on UUO model in rat are comparable with the well-known RAS inhibitors captopril and losartan.
肾素-血管紧张素系统（RAS）在单侧输尿管梗阻（UUO）后肾损伤的病理生理学中起着核心作用，这一点已得到充分证实。本研究探讨了胸腺醌和 RAS 阻断对单侧输尿管梗阻大鼠肾组织损伤和肾组织血管紧张素 II 表达的影响。
40 只雄性大鼠分为五组：假手术组、UUO 组和 UUO 大鼠用氯沙坦、卡托普利和胸腺醌治疗。UUO 后两周，通过测量肾氧化应激、细胞凋亡以及肿瘤坏死因子-α（TNF-α）、单核细胞趋化蛋白-1（MCP-1）和血管紧张素 II 的表达来评估大鼠。
UUO 后两周，肾细胞凋亡数量和肾丙二醛及 TNF-α表达显著增加。此外，与假手术组相比，UUO 组肾总巯基含量和抗氧化酶活性显著降低。此外，UUO 与阻塞肾中血管紧张素 II 和 MCP-1 的表达上调有关。与 UUO 组相比，氯沙坦、卡托普利和胸腺醌显著改善了氧化损伤、细胞凋亡和 TNF-α表达，并显著降低了血管紧张素 II 和 MCP-1 的上调。
本研究表明，胸腺醌能够改善 UUO 引起的肾组织损伤。胸腺醌对大鼠 UUO 模型的这些有利作用与众所周知的 RAS 抑制剂卡托普利和氯沙坦相当。
