Efectos de la dexmedetomidina en conjunto con el precondicionamiento isquémico remoto en la lesión de isquemia-reperfusión renal en ratones

Emine Bagcik , Sevda Ozkardesler , Nilay Boztas , Bekir Ugur Ergur , Mert Akan , Mehmet Guneli , Sule Ozbilgin
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Abstract

Background and objectives

The aim of this study was to evaluate the effects of remote ischemic preconditioning by brief ischemia of unilateral hind limb when combined with dexmedetomidine on renal ischemia-reperfusion injury by histopathology and active caspase-3 immunoreactivity in rats.

Methods

28 Wistar albino male rats were divided into 4 groups. Group I (Sham, n = 7): laparotomy and renal pedicle dissection were performed at 65th minute of anesthesia and the rats were observed under anesthesia for 130 min. Group II (ischemia-reperfusion, n = 7): at 65th minute of anesthesia bilateral renal pedicles were clamped. After 60 min ischemia 24 h of reperfusion was performed. Group III (ischemia-reperfusion + dexmedetomidine, n = 7): at the fifth minute of reperfusion (100 μg/kg intra-peritoneal) dexmedetomidine was administered with ischemia-reperfusion group; reperfusion lasted 24 h. Group IV (ischemia-reperfusion + remote ischemic preconditioning + dexmedetomidine, n = 7): after laparotomy, three cycles of ischemic preconditioning (10 min ischemia and 10 min reperfusion) were applied to the left hind limb and after 5 min with group iii.

Results

Histopathological injury scores and active caspase-3 immunoreactivity were significantly lower in the Sham group compared to the other groups. Histopathological injury scores in groups iii and iv were significantly lower than group ii (P = .03 and P = .05). Active caspase-3 immunoreactivity was significantly lower in the group iv than group ii (P = .01) and there was no significant difference between group ii and group iii (P = .06).

Conclusions

Pharmacologic conditioning with dexmedetomidine and remote ischemic preconditioning when combined with dexmedetomidine significantly decreases renal ischemia-reperfusion injury histomorphologically. Combined use of two methods prevents apoptosis via active caspase-3.

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右美托咪定联合远程缺血预处理对大鼠肾缺血再灌注损伤的影响
背景与目的通过组织病理学和活性caspase-3免疫反应性观察单侧后肢短暂缺血远程缺血预处理联合右美托咪定对大鼠肾缺血再灌注损伤的影响。方法28只雄性Wistar白化大鼠随机分为4组。第一组(Sham, n = 7):麻醉第65分钟开腹,解剖肾蒂,麻醉观察130 min。第二组(缺血-再灌注,n = 7):麻醉第65分钟夹持双侧肾蒂。缺血60 min后进行24 h再灌注。III组(缺血-再灌注+右美托咪定,n = 7):缺血-再灌注组在再灌注第5分钟给予右美托咪定(100 μg/kg腹腔注射);再灌注持续24 h。IV组(缺血-再灌注+远程缺血预处理+右美托咪定,n = 7):开腹后,左后肢进行3个周期的缺血预处理(缺血10 min,再灌注10 min), iii组术后5 min。结果Sham组大鼠病理损伤评分和活性caspase-3免疫反应性明显低于其他各组。iii、iv组的组织病理学损伤评分均显著低于ii组(P = 0.03、P = 0.05)。iv组活性caspase-3免疫反应性显著低于ii组(P = 0.01), ii组与iii组间差异无统计学意义(P = 0.06)。结论右美托咪定的药理调节和联合右美托咪定的远程缺血预处理在组织学上可显著减轻肾缺血再灌注损伤。两种方法联合使用可通过活性caspase-3阻止细胞凋亡。
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