缺血后处理增加脊髓miR-125b表达减轻大鼠脊髓缺血-再灌注损伤后神经元凋亡

目的观察缺血后处理(Ischemic postconditioning,IPC)对大鼠脊髓缺血再灌注损伤(Spinal cord ischemia reperfusion injury,SCIRI)后microRNA(miRNA,miR)-125b表达及下肢运动功能的影响。方法 45只SD大鼠平均随机分为3组:假手术组(Sham组)、缺血-再灌注组(IR组)和缺血后处理组(IPC组)。Sham组仅暴露主动脉弓而不夹闭,其他各组夹闭主动脉弓14 min后再开放建立SCIRI模型。IPC组于再灌注5 min后给予5循环缺血后适应。再灌注后24 h,处死大鼠,提取脊髓组织,分别检测脊髓组织湿/干重比(Wet-dry ratio,W/D)和总含水量(Total water content,TWC),HE染色观察脊髓组织病理学变化,qRT-PCR测定脊髓组织中miR-125b表达,TUNEL法检测神经元凋亡数量(Apoptotic quantitiy,AQ)。结果术后24 h,与Sham组比较,IR组大鼠脊髓W/D、TWC、AQ升高,脊髓组织中miR-125b表达下调(P<0.05);与IR组比较,IPC组脊髓W/D、TWC、AQ降低,脊髓组织中miR-125b表达上调(P<0.05)。HE染色显示,Sham组脊髓前角结构完好,可见大量胞核完整的运动神经元,IR组脊髓前角内大量空泡形成,神经元结构缺失,胞质呈嗜酸性,而IPC组脊髓前角存在部分结构正常的神经元。结论缺血后处理可能通过上调脊髓组织中miR-125b的表达,减少脊髓组织前角运动神经元凋亡,从而改善大鼠SCIRI损伤。

Ischemic postconditioning alleviates neuronal apoptosis after spinal cord ischemia reperfusion injury by increasing spinal microRNA-125b expression in rats

Objective To observe the effects of ischemic postconditioning (IPC) on expressions of microRNA (miRNA,miR)-125b and lower limb motor function after spinal cord ischemia reperfusion injury (SCIRI) in rats.Methods Forty-five rats were divided into three groups:sham group (n=15),IR group (n=15),and IPC group (n=15).Aortic arch was only exposed but not occluded in rats of sham group.SCIRI was established by aortic arch occlusion for 14 min.IPC was induced by 5 cycles of ischemic adaptation at 5 min after reperfusion.At 24 h after reperfusion,spinal cord was extracted to determine the spinal wet-dry ratio (W/D) and total water content (TWC).Changes of spinal morphology and neuronal apoptotic quantitiy (AQ) were detected by HE and TUNEL staining,respectively.miR-125b expression was assessed by qRT-PCR.Results Compared with sham group,rats in IR group and IPC group had significantly higher W/D,TWC and AQ,but lower miR-125b expression at 24 h after SCIRI (P<0.05).Compared with IR group,rats in IPC group had lower W/D,TWC and AQ,but higher miR-125b expression (P<0.05).As showed in represented HE staining,the neuronal morphologies in sham group were intact with integrated nucleus.But in IR group,a large number of vacuoles and absent of structure were formed in neurons of anterior horn,and the cytoplasm was eosinophilic.There were still some neurons with normal structure left in IPC group.Conclusion Ischemic postconditioning can decrease the neuronal apoptosis in anterior horn and further alleviate SCIRI by increasing the spinal miR-125b expression