缺血后处理对脑缺血再灌注损伤后ERK1/2和Akt磷酸化及神经细胞凋亡的影响

Effects of Ischemic Post-condtioning on Activation of ERK1/2 and Akt and Neuronal Apoptosis in Rats with Cerebral Ischemia Reperfusion Injury

目的:观察缺血后处理对大鼠局灶性脑缺血再灌注损伤后ERK1/2和Akt及神经细胞凋亡的影响。方法:成年健康SD大鼠72只,随机分为假手术(sham)组、缺血再灌注(I/R)组、缺血后处理(Postcond)组各24只,应用线栓法建立大脑中动脉闭塞(MCAO)再灌注模型。分别于再灌注10min、30min、6h、24h后留取大脑皮质。Western blot检测再灌注10min、30min、6h后ERK1/2和Akt活性变化;原位末端标记(TUNEL)检测再灌注后24h神经细胞凋亡。结果:Postcond组再灌注10min、30min、6h后ERK1/2和Akt活性高于I/R组(P<0.05);脑缺血再灌注24h后,Postcond组与I/R组比较,TUNEL阳性细胞减少(P<0.05)。结论:缺血后处理可提高大鼠脑缺血再灌注后皮质内ERK1/2和Akt活性,减少神经细胞凋亡。

Objective： To investigate the effects of ischemic post-condtioning on ERK1/2 and Akt activation and neuronal apoptosis in rats with cerebral ischemia reperfusion injury.Methods： SD rat with focal ischemic reperfusion was induced by intraluminal middle cerebral artery occlusion（MCAO） with a nylon monofilament suture.Ischemic animals were randomly assigned to 3 groups（n=24）,the sham group,I/R group and Postcond group.In Postcond group,the animals with MCAO were further subject to postconditioning（6 cycles of 30s ischemia and 30s reperfusion） after MCAO.The phosphorylation of Akt and ERK1/2 in the cortex was measured by Western Blot.The neuronal apoptosis was detected by TUNEL staining.Results： Postcond treatment significantly increased phosphorylation of Akt and ERK1/2 at 10 min,30 min,and 6 h after reperfusion.At 24 h after reperfusion,the rats in the Postcond group showed much less TUNEL positive cells in the cortex than those in the I/R group.Conclusion：Ischemic post-conditioning decreases apoptosis and improves neurological functions,perhaps which by increasing levels of Akt and ERK1/2 activation in cerebral I/R injury.