Effect of propofol pretreatment on the expression of p-JNK, MMP-9 and AQP-4 during focal cerebral isch- emin-reperfusion in rats

Abstract

Objective To investigate the effect of propofol pretreatment on the expression of phosphorylated c-Jun N-terminal kinase （p-JNK）, matrix metalloproteinase-9 （MMP-9） and aquaporin-4 （AQP-4） during focal cerebral ischemia-reperfusion （I/R） in rats. Methods Seventy-two healthy male SD rats weighing 250-280 g were randomly divided into 4 groups （n = 18 each）： sham operation group （group S）, I/R group and propofol pretreatment group （P1 and P2）. In group I/R, P1 and P2, focal cerebral I/R was induced by occlusion of middle cerebralartery for 2 h followed by 24 h of reperfusion. In group P1 and P2, intraperitioneal 0.5 % and 1% propofol 10 ml/kg were injected 30 rmin before ischemia respectively. In group I/R, normal saline 10 ml/kg was given instead of propofol 30 min before ischemia. Neurological deficit score （NDS） was assessed after consciousness was recovered. 2% Evans blue （EB） 3 ml/kg was injected intravenously 1 h before the animals were sacrificed at 24 h of reperfusion. The brain tissues were taken for determination of the brain water content, EB content and expression of p-JNK, MMP-9 and AQP-4. Results Compared with group S, the NDS and content of water and EB were significantly increased and the expression of p-JNK, MMP-9 and AQP-4 was up-regulated in group I/R, P1 and P2（P 〈 0.05）. Compared with group I/R, the NDS and content of water and EB were significantly decreased and the expression of p-JNK, MMP-9 and AQP-4 was down-regulated in group P1 and P2 （P 〈 0.05）. Compared with group P1 , the expression of p-JNK and MMP-9 was down-regulated （P 〈 0.05）, but no significant difference was found in the NDS, water and EB content and the expression of AQP-4 in group P2 （P 〉 0.05）. Conclusion Propofol pretreatment can reduce focal cerebral I/R injury by inhibiting the activation of JNK signal pathway and up-regulation of MMP-9 and AQP-4 expression. Key words: Propofol; Reperfusion injury; Brain; JNK mitogen-activated protein kinases; Matrix metalloproteinase 9; Aquaporin 4