| INTRODUCTIONMitogen - activated protein kinases (MAPKs) have crucial roles in signal transduction from the cell surface to the nucleus and regulate cell death and survival. Recent papers support the hypothesis that neuronal apoptosis and cerebral ischemia induce the robust activation of MAPK cascades. Although extracellular signal - regulated kinases pathways promote cell survival and proliferation, and c - Jun N - terminal protein kinases/p38 pathways induce apoptosis in general, the roles of MAPK cascades in neuronal death and survival seem to be complicated and altered by the type of cells and the magnitude and timing of insults. Some specific inhibitors of MAPK cascades provide important information in clarifying the roles of each molecule in neuronal death and survival, but the results are still controversial. Further studies are necessary to elucidate the activated signal transduction upstream and downstream of the cascades in cerebral ischemia, and to define the crosstalk between the cascades and other signaling pathways, before MAPK cascades can be candidate molecules in the treatment of cerebral ischemia.Naloxone has been advanced as a potential neuroprotectant against ischemic injury. If is naloxone, acting through a blockade of mu opioid receptor activation , beneficial to cerebral I/R insult in terms of reducing brain infarction, neu-trophil accumulation, and chemokine expression. and how dose it play the role through the MAPK system this article will tell us about it.MATERIALS AND METHODSWistar rats were supplied from Department of Laboratory Animals , China Medical University TheERKl/2 and p38 antibodies were obtained from Santa CruzMethodsForty five male Wistar rats weighting 300 — 350g were randomly divided into 9 groups: group A sham - operated ( n = 5 );group B I/R (n = 5) including subgroups BlxB2%B3xB4 according to time of I/R( B, 8hrs;B2lday;B3 3days%B4 5days;group C group (n =5) naloxone -given intraperitoneal 10 min before global cerebral I/R (lmg/kg ) including sbugroups C1%C2>C3XC4 according to the condition of group B. Global cerebral I/R was produced by 4 -vessel occlusion method. Bilateral carotid arteries were released for reperfusion after 10 min cerebral ischemia. The animals were decapitated at the end of 8h,ld,3d,5d reperfusion and brains were removed The expression of ERKl/2 and P38 protein in the hippocampus were determined by Western Blotting methodResultsI/R induced significant increase in the expression of ERKl/2 and P38 protein in group B as compared to group A . Intraperitoneal naloxone treatment significantly inhibited the increase in ERKl/2 and P38 protein expression induced by global cerebral I/R.DiscussionMitogen - activated protein kinases ( MAPKs) have crucial roles in signal transduction from the cell surface to the nucleus and regulate cell death and survival. Recent papers support the hypothesis that neuronal apoptosis and cerebralischemia induce the robust activation of MAPK cascades. Although extracellular signal - regulated kinases pathways promote cell survival and proliferation, and c - Jun N - terminal protein kinases/p38 pathways induce apoptosis in general, the roles of MAPK cascades in neuronal death and survival seem to be complicated and altered by the type of cells and the magnitude and timing of insults. Some specific inhibitors of MAPK cascades provide important information in clarifying the roles of each molecule in neuronal death and survival, but the results are still controversial. Specific mechanisms can be considered from three aspects:1. Opiate - Passing through internal factors role in curbing the further suppression of brain blood to recharge because of the lack of oxygen resulted in the excitement of monosodium release significant increase in ERK and reduced monosodium P38 impact.2. The flow through effect of Ca +, reducing cell Ca + overloading, and further reduce the impact of MAPK enzyme. Because MAPK system through inter — cell channels to cell growth, multiplication, Diaowang impact. Internal environment through reduced regulation of the nerve cell damage.3. Opiate - Passing through suppression of origin to regulate and control the NMDA receptors, MAPK reduced to the role of NMDA. ERK and P38 data obtained from the two sets of information analysis, opiate - driven system to the impact MAPK system, the protein expressed in 3d view, the role of P38 Group conditioning back stronger ERK group. These results indicate a strong in the path of ERK MAPK ways to impact significantly weaker P38 Diaowang ways, the conclusions are consistent with literature reports, the regulation of P38 is the focus of our study.Conclusionlobal cerebral I/R induces significant increase in the expression of ERK1/ 2 and P38 protein.Naloxone treatment can significantly inhibit I/R induced increase in expression of ERK1/2 and P38. |
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