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血管紧张素 II 型受体阻滞剂 PD123319 比氯沙坦对缺血再灌注损伤和氧化损伤的保护作用更强。

Angiotensin II type 2 receptor blocker PD123319 has more beneficial effects than losartan on ischemia-reperfusion injury and oxidative damage in isolated rat heart.

机构信息

Department of Physiology, Faculty of Medicine, Bezmialem Vakif University, 34093 Fatih, Istanbul, Turkey.

Institute of Graduate Studies in Science and Engineering, Istanbul University, 34134 Fatih, Istanbul, Turkey.

出版信息

Can J Physiol Pharmacol. 2019 Dec;97(12):1124-1131. doi: 10.1139/cjpp-2019-0076. Epub 2019 Jul 30.

Abstract

Our study aimed to determine the effects of losartan and PD123319 in ischemia-reperfusion (IR) injury in isolated perfused rat heart. The study used 40 male Wistar albino rats that were grouped as Control, IR, and IR treatment groups that received losartan (20 mg/kg), PD123319 (20 mg/kg), and losartan+PD123319. The hearts were attached to Langendorff isolated heart system by employing in situ cannulation method, and cardiodynamic parameters were recorded during the experiment. At the end of experiment, hearts were retained for biochemical analysis and all data were statistically evaluated. A partial recovery of cardiodynamic parameters was observed in all treatment groups. A significant increase in oxidative stress parameters were seen in the IR group, whereas all treatment groups exhibited lower increase. Furthermore, levels of all antioxidant parameters were significantly lower in the IR group, but higher in the treatment groups. Effects on all parameters were much more remarkable in the PD123319 group. Levels of angiotensin II and renin were increased ( < 0.001) with IR application and decreased ( < 0.001) with the treatment of both antagonists. In conclusion, treatment of losartan and PD123319 played a cardioprotective role against IR injury, PD123319 being more effective in this protection.

摘要

我们的研究旨在确定氯沙坦和 PD123319 在缺血再灌注(IR)损伤中的作用在分离灌注的大鼠心脏。该研究使用了 40 只雄性 Wistar 白化大鼠,分为对照组、IR 组和 IR 治疗组,分别给予氯沙坦(20mg/kg)、PD123319(20mg/kg)和氯沙坦+PD123319。采用原位插管法将心脏连接到 Langendorff 分离心脏系统,并在实验过程中记录心动力学参数。实验结束时,保留心脏进行生化分析,所有数据均进行统计学评估。所有治疗组均观察到心动力学参数的部分恢复。IR 组的氧化应激参数显著增加,而所有治疗组的增加幅度较低。此外,IR 组的所有抗氧化参数水平显著降低,但治疗组的水平较高。PD123319 组对所有参数的影响更为显著。血管紧张素 II 和肾素水平随着 IR 应用而升高(<0.001),随着两种拮抗剂的治疗而降低(<0.001)。总之,氯沙坦和 PD123319 的治疗对 IR 损伤具有心脏保护作用,PD123319 在这种保护中更为有效。

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