The Effects Of P38MAPK Signal Transduction Pathway In Cerebral Protection Of Limb Ischemic Preconditioning

Objective:To study the cerebral protective effects of noninvasive remote limb ischemic preconditioning(RLIP) against ischemia-reperfusion injury using the middle cerebral artery occlusion in rats and to investigate whether through lowering p38 MAPK signal transduction pathway activity to reduce the apoptosis of nerve cells contributes to cerebral protection.Methods:Thirty-six healthy male Sprague-Dawley rats(weight 200-250g) were randomly divided three groups(n=12,each group):sham-operated group(sham group)、I/R group、RLIP group.In the sham group,only seperate common carotid artery(CCA)、internal carotid artery(ICA)and external carotid artery(ECA),but don,t block the blood flow.In the I/R group,rats were subjected to 2h of right middle cerebral artery occlusion(MCAO)followed by 24 h of reperfusion.In the RLIP group,rats were accepted 3 cycles of 5 minutes ischemia followed by 5 minutes reperfusion on right hind limb at the beginning of MCAO.Evalution of neurologic deficit scores was performoned on 24 h after reperfusion by the method of Longa,s.Six rats were randomly selected to measure the cerebral infarction volume by TTC staining and another rats were observed tissue morphology of hippocampal CA1 region by HE staining.The expression of P-p38MAPK、Caspase8 and Caspase3 in the hippocampal CA1 region were determined by immunohistochemical analysis.Results:1、There was no neurologic deficit in sham group.The NDS in RLIP group was lower than that in I/R,but there was no significant difference between them.2 、 TTC staining :There was no infarction volume in sham group,The cerebral infarction volume in RLIP group decreased significantly comparing with that in I/R group(P<0.05).3 、 HE staining showed that in the sham group,the pyramidal neuron of hippocampal CA1 region were aligned 、dense,for 2-3 layers,its shape was normal and its cell nucleus was round and big,dyed in light blue.But the pyramidal neuron in the I/R group were dyed deepen,its number reduced significantly, its volume shrinked and its cell nucleus were fragmentized and dissoved. And compared with that in I/R group,the hippocampal pyramidal neuron in RLIP group were more integrated and clear.4 、 Immunohistochemical analysis:the expression of P-p38 MAPK 、 Caspase8 and Caspase3 protein obviously down-regulated than that in I/R group(P<0.05),but they were up-regulated significantly than that in shamgroup(P<0.05).Conclusions:Noninvasive romote limb ischemic preconditioning has protective effects against cerebral ischemia-reperfusion injury which may related to reducing apoptosis of neurons by p38 MAPK signal transduction pathway.