Effect of Le Er Mai on the Inflammatory Response in Hippocampial Tissue of Cerebral Ischemia Reperfusion Injuried Rats

OBJECTIVE To study the effects of Le Er Mai(LEM) on inflammatory response in hippocampial tissue of cerebral ischemia reperfusion (CIR) in rats. METHODS A CIR injuried model was produced using middle cerebralartery occlusion (MCAO) . The rat brain containing water was detected by drying test, and the cerebral infarct area was measureed by 2,3,5-triphenlytetrazolium chloride (TTC). The chemistry method and I-125 radio-immunity method were employed to determine the content of MDA, lactate (LD), tumor necrosis factor (TNF-α) and interneuckin-6 (IL-6) in hippocampus tissue. The expression of minocyte chermoattractant protein-1mRNA (MCP-1 mRNA), cyclooxygenase-2mRNA,(COX-2 mRNA), and matrix metalloproteinase-2,3,9 mRNA(MMP-2,9,13 mRNA) were examined by RT-PCR.The expression of mitogen activated protein kinase (P38MAPK), phosphorylation mitogen activated protein kinase (P-P38MAPK), nuclear factor-kappa-κB (NF-κB), phosphorylation nuclear factor-kappaB (P-NF-κB), inhibitory-κB (IκB), phosphorylation inhibitory-κB (P-IκB) and transcription factor (c-fos, c-jun ) were detected by Western blod. RESULTS Ler Er Mai and Flunarizinum alleviated the brain edemal and brain infarct area in cerebral ischemia reperfusion rats, and the contents of IL-6, TNF-α, MDA and LD were markedly decreased in hippocampus tissue. The expressions of P-38MAPK and P-38MAPK in hippocampus of CIR rats were augmented in compared with sham-operated rats, and the brain tissue containing water and CIR infarct area were significantly increased. The apoptosis rate of hippocampus neuronal in CIR model were increased, and blood brain barrier were impaired. Besides, the expression of MMP-2, MMP-13, MCP-1, COX-2 mRNA were upregulated in ischemia 2h after reperfusion 3d in rats model group. In compared with CIR model group, LEM and Flunarizinum treatment groups, the expression of MMP-2,13mRNA were downregulated and neuronal apoptosis was attenuated. CONCLUSION Cytokine and medium were released in hippocampus induced by cerebral ischemia reperfusion activating p38MAPK and NF-κB/IκB signaling transcription pathway cascades reaction. Mcp-1, COX-2, and MMP-2,9,13mRNA transcription were increased, IL-6, TNF-α, MDA, LD synthesis were augmented, conducing brain edema and brain infarct area amplification. The effect of LEM on inhibition of the hippocampus tissue cell liberating inflammatory medium induced by CIR may be related to inhibitetion the activation of p38MAPKand NF-κB/IκB signaling pathway.