Evaluation of the Effects of Atorvastatin and Ischemic Postconditioning Preventing on the Ischemia and Reperfusion Injury: Experimental Study in Rats

Abstract Introduction: Reperfusion injury leads to systemic morphological and functional pathological alterations. Some techniques are already estabilished to attenuate the damage induced by reperfusion. Ischemic preconditioning is one of the standard procedures. In the last 20 years, several experimental trials demonstrated that the ischemic postconditioning presents similar effectiveness. Recently experimental trials demonstrated that statins could be used as pharmacological preconditioning. Methods: 41 Wistar rats (Rattus norvegicus albinus) were distributed in 5 groups: Ischemia and Reperfusion (A), Ischemic Postconditioning (B), Statin (C), Ischemic Postconditioning + Statins (D) and SHAM (E). After euthanasia, lungs, liver, kidneys and ileum were resected and submitted to histopathological analysis. Results: The average of lung parenchymal injury was A=3.6, B=1.6, C=1.2, D=1.2, E=1 (P=0.0029). The average of liver parenchymal injury was A=3, B=1.5, C=1.2, D=1.2, E = 0 (P<0.0001). The average of renal parenchymal injury was A=4, B=2.44, C=1.22, D=1.11, E=1 (P<0.0001). The average of intestinal parenchymal injury was A=2, B=0.66, C=0, D=0, E=0 (P=0.0006). The results were submitted to statistics applying Kruskal-Wallis test, estabilishing level of significance P<0.05. Conclusion: Groups submitted to ischemic postconditioning, to pre-treatment with statins and both methods associated demonstrated less remote reperfusion injuries, compared to the group submitted to ischemia and reperfusion without protection.

摘要 引言：再灌注损伤可引发全身性的形态学与功能学病理改变。目前已有多项成熟技术可减轻再灌注诱导的组织损伤。缺血预处理（Ischemic preconditioning）即为其中一项标准干预手段。近20年来，多项实验研究证实缺血后处理（Ischemic Postconditioning）具有相似的组织保护效果。近期亦有实验研究表明，他汀类药物（statins）可作为药物预处理方案应用于该领域。

方法：本研究纳入41只Wistar大鼠（Rattus norvegicus albinus），将其分为5组：缺血再灌注组（A组）、缺血后处理组（B组）、他汀干预组（C组）、缺血后处理联合他汀干预组（D组）以及假手术组（E组）。处死大鼠后，摘取肺、肝、肾及回肠组织，行组织病理学分析。

结果：肺实质损伤平均评分依次为A组3.6、B组1.6、C组1.2、D组1.2、E组1（P=0.0029）；肝实质损伤平均评分依次为A组3、B组1.5、C组1.2、D组1.2、E组0（P<0.0001）；肾实质损伤平均评分依次为A组4、B组2.44、C组1.22、D组1.11、E组1（P<0.0001）；肠实质损伤平均评分依次为A组2、B组0.66、C组0、D组0、E组0（P=0.0006）。本研究采用Kruskal-Wallis检验进行统计学分析，设定显著性检验水准为P<0.05。

结论：相较于未接受任何保护干预的缺血再灌注组，接受缺血后处理、他汀类药物预处理以及二者联合干预的各组，其远隔器官再灌注损伤程度均显著降低。