Guan Weiwei, Wang Zhen, Liu Yukai, Han Yu, Ren Hongmei, Eric Wang Wei, Yang Jian, Zhou Lin, Zeng Chunyu
Department of Cardiology, Daping Hospital, The Third Military Medical University, 400042 Chongqing, China; Chongqing Institute of Cardiology, 400042 Chongqing, China.
Department of Cardiology, Daping Hospital, The Third Military Medical University, 400042 Chongqing, China; Chongqing Institute of Cardiology, 400042 Chongqing, China.
Eur J Pharmacol. 2015 Aug 15;761:144-52. doi: 10.1016/j.ejphar.2015.05.009. Epub 2015 May 14.
Tirofiban, a glycoprotein IIb/IIIa receptor inhibitor, is widely used in the management of patients with unstable angina or myocardial infarction, and shows protective effects on ischemia/reperfusion (I/R) injured heart. Whether or not it has protective effect on I/R injured kidney is not known. The present in vivo and in vitro study found that serum creatinine (SCR) and blood urea nitrogen (BUN) were significantly increased in I/R rats, accompanied by histopathological damage of the kidney. Apoptotic cells, leukocyte infiltration and ROS production were increased in I/R rats. Pretreatment by intravenous injection of tirofiban (200μg/kg) reduced SCR and BUN levels, ameliorated renal histopathological changes, and decreased ROS production, cell apoptosis and leukocyte infiltration in I/R injured kidney. Our further study showed that the protection of tirofiban might be associated with the restoration of eNOS/iNOS balance, since inhibition of NO production blocked the tirofiban-mediated renal protection on I/R injury. The present in vivo and in vitro study indicated that tirofiban pretreatment exerts a protective effect on I/R injury in kidney through regulation of eNOS/iNOS balance.
替罗非班是一种糖蛋白IIb/IIIa受体抑制剂,广泛用于不稳定型心绞痛或心肌梗死患者的治疗,并对缺血/再灌注(I/R)损伤的心脏具有保护作用。其对I/R损伤的肾脏是否具有保护作用尚不清楚。目前的体内和体外研究发现,I/R大鼠的血清肌酐(SCR)和血尿素氮(BUN)显著升高,同时伴有肾脏组织病理学损伤。I/R大鼠的凋亡细胞、白细胞浸润和活性氧生成增加。静脉注射替罗非班(200μg/kg)预处理可降低SCR和BUN水平,改善肾脏组织病理学变化,并减少I/R损伤肾脏中的活性氧生成、细胞凋亡和白细胞浸润。我们的进一步研究表明,替罗非班的保护作用可能与恢复eNOS/iNOS平衡有关,因为抑制一氧化氮生成可阻断替罗非班对I/R损伤的肾脏保护作用。目前的体内和体外研究表明,替罗非班预处理通过调节eNOS/iNOS平衡对肾脏I/R损伤发挥保护作用。