| Aim: To investigate the effects and mechanism of PDTC, a nuclearfactor-κB inhibitor, on neuron injury in global cerebral ischemiareperfusion (GCIR) rat hippocampus.Methods: GCIR rat model was established by bilateral commoncarotid arteries occlusion and systemic hypotension. Spatial learning andmemory function of rats was tested using Morris water maze. Pathologicalchanges of hippocampal neurons was observed by HE staining. Expressionof COX2mRNA was measured by RT-PCR. NF-κB and COX2proteinwere detected by immunohistochemistry. Content of PGI2and TXA2in therat hippocampus were detected by enzyme-linked immunosorbent assay.Results: A significant increase of escape latency was observed in theGCIR group rats compared to the sham operation group（P<0.05）.Hippocampal neurons in GCIR group rats showed obvious damage during15d. The expression of NF-κB was significantly increased in the GCIRgroup rat hippocampus from30min to15d and reached the peak at24h（P﹤0.01）. Treatment of GCIR induced a significant increase of COX2mRNA expression from2h to15d with a peak of48h（P﹤0.05）, and theCOX2protein expression significantly increased from2h to15d andreached the peak on7d. PGI2/TXA2has a significant increase during15d,reached its peak at48h. At day12after reperfusion, PDTC pretreatmeant(PDTC100mg kg-1or200mg kg-1was injected ip at one hour before ischemia respectively) significantly reduced escape latency（P<0.05）andhistopathological injury in CA1region of GCIR rat hippocampus. EitherPDTC100mg·kg-1or PDTC200mg·kg-1reduced NF-κB and COX2expression, PGI2content, TXA2content and PGI2/TXA2on day12.Conclusions: Expression and activation of NF-κ B can upregulate theexpression of COX2and PGI2/TXA2, which maybe participate inregulation of pathophysiological process of cerebral injury induced byGCIR. PDTC can protect hippocampus from global cerebral ischemiareperfusion injury through inhibition of NF-κB, COX2expression andPGI2/TXA2, and this protect effect maintaining at least12days. |
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