远程缺血预处理对兔脊髓缺血再灌注损伤的保护作用及其机制

Protective effect of remote ischemic preconditioning on spinal cord ischemia reperfusion injury and its possible mechanism in a rabbit model

目的探讨远程缺血预处理(RIPC)对兔脊髓缺血再灌注损伤(SCIRI)的保护作用及其机制。方法 36只日本大耳白兔随机双盲均分为假手术组(S组)、缺血再灌注损伤组(IR组)、IR+RIPC组,每组12只动物。S组不阻断腹主动脉,IR组和IR+RIPC组夹闭腹主动脉30 min建立SCIRI模型,IR+RIPC组于主动脉阻断前1 h实施RIPC。三组动物在再灌注2 d和5 d行后肢神经功能评分后处死并取脊髓组织L3~L5段,评估病理学变化;同时检测SOD1活性和SOD1 m RNA的表达水平。结果同一时间点,IR组后肢神经功能评分和脊髓组织病理切片分级与S组相比,显著降低(P<0.01);而IR+RIPC组后肢神经功能评分和脊髓组织病理切片分级与IR组相比,则明显改善,差异均有高度统计学意义(P<0.01);术后第2天,与S组比较,IR+RIPC组SOD1活性和SOD1m RNA的表达水平均显著升高,差异均有高度统计学意义(P<0.01),而IR组则无明显变化(P>0.05);术后第5天,与S组比较,IR组SOD1活性和SOD1 m RNA的表达水平均显著降低,差异均有高度统计学意义(P<0.01),而IR+RIPC组则无明显变化(P>0.05);与IR组比较,IR+RIPC组SOD1活性和SOD1 m RNA的表达水平均显著升高,差异均有高度统计学意义(P<0.01);IR组、IR+RIPC组脊髓组织SOD1 m RNA表达变化与SOD1活性的变化呈正相关(R=0.96、0.97,均P<0.01)。结论 RIPC对兔SCIRI有一定的防治作用,其机制与增强脊髓组织缺血性损伤区域中SOD1的表达有关。

Objective To investigate the protective effect of remote ischemic preconditioning(RIPC)on spinal cord ischemia reperfusion injury(SCIRI)and its possible mechanism in a rabbit model.Methods Thirty-six rabbits were randomly divided into sham operation group(Sham group),ischemia reperfusion group(IR group),IR+RIPC group,12 rats in each group.On the 2 sec and 5th day after reperfusion,6 animals were sacrificed respectively.Animals in Sham group were exposed abdominal aorta(without interruption),IR group and IR+RIPC group received abdominal aortic clamp 30 min,and established SCIRI model.IR+RIPC group underwent RIPC before aortic clamp 1 h.All animals were evaluated for hindlimb function scores in postoperative 2 days and 5 days,according to the Tarlov standard,and then were sacrificed and the L3-L5 segment of the spinal cord were detected to observe the pathological changes of spinal cord tissues.Meanwhile,the SOD1 activity and the expression level of SOD1 mRNA were detected.Results On the same timepoint,compared with the Sham group,the neurological function scores and pathological grading of spinal cord tissue in IR group were significantly decreased(P<0.01),but compared with the IR group,the neurological function scores and pathological grading of spinal cord tissue in IR+RIPC group were significantly improved(P<0.01).On the second day after operation,compared with the Sham group,the activity of SOD1 and the expression level of SOD1 mRNA in the IR+RIPC group were all significantly increased(P<0.01),whereas there was no significant change in the IR group(P>0.05).On the 5th day after operation,compared with the Sham group,the activity of SOD1 and the expression level of SOD1 mRNA in the IR group were all significantly decreased(P<0.01),and there was no significant change in the IR+RIPC group(P>0.05).Compared with IR group,the SOD1 activity and the expression level of SOD1 mRNA were all significantly increased in the RIPC group(P<0.01).The change of SOD1 mRNA expression in spinal cord was positively related to the change of SOD1 activity in IR group or IR+RIPC group(R=0.96 or 0.97,all P<0.01).Conclusion RIPC has a certain preventive effect on rabbit SCIRI,and its mechanism is related to enhancing the expression of SOD1 in ischemic region of spinal cord tissues.