摘要
目的探讨大鼠局灶性脑缺血再灌注时核因子κB(NFκB)、白细胞介素1(IL1)、肿瘤坏死因子α(TNFα)、细胞间黏附分子1(ICAM1)在异丙酚脑保护机制中的作用。方法对90只雄性Wistar大鼠,采用大脑中动脉线栓法建立局灶性脑缺血再灌注模型,并随机将大鼠分为假手术组、缺血再灌注组和异丙酚组,每组30只。在大鼠脑缺血2h后进行再灌注。在再灌注2、6、12、24h,应用免疫组织化学染色分析核因子κB的移位,蛋白质印迹检测大鼠脑组织中核核因子κB的表达量。在再灌注3、6、24、72h,采用免疫组织化学染色检测脑组织IL1、TNFα、ICAM1的表达。结果局灶性脑缺血再灌注后,核因子κB在再灌注2～24h明显从细胞浆移位于细胞核内,与假手术组比较,核因子κB的表达量显著增加,灰度值分别为86±10、89±9、87±10、94±8(均P<001),IL1、TNFα、ICAM1表达的峰值明显升高,灰度值分别为170±5、174±5、171±4(均P<001),但在时间上明显滞后于核核因子κB。应用异丙酚,脑缺血再灌注后核因子κB从细胞浆向细胞核的移位被明显抑制,与缺血再灌注组比较,核因子κB的表达量显著减少,灰度值分别为61±6、62±5、66±6、63±7(均P<005),IL1、TNFα、ICAM1表达的峰值明显降低,分别为150±4、152±5、152±4(均P<005)。结论异丙酚能抑制大鼠局?
Objective To investigate the effect of propofol on the activation of nuclear factor κB (NF κB) and the expression of inflammatory cytokines, such as interleukin 1 (IL 1), tumor necrosis factor α (TNF α), and intercellular adhesion molecule 1 (ICAM 1) in cerebral cortex during transient focal cerebral ischemia reperfusion,and to discuss the probable mechanism of its protective effect. Methods Ninety male Wistar rats were randomly divided into 3 equal groups: sham operation group undergoing sham operation; ischemia/reperfusion (I/R) group undergoing thread embolism of the left middle cerebral artery occlusion (MCAO) to cause focal ischemia for 2 hours and then undergoing reperfusion; and propofol group undergoing peritoneal injection of propofol 2 hours before the ischemia reperfusion of MCAO. Then the rats in the 3 groups were re divided into subgroups of 5 rats, totally 18 subgroups, to be decapitated 2, 3, 6, 12, 24, and 72 hours after reperfusion for the latter 2 groups, and their brains were taken out and fixed. Immunohistochemistry was used to detect the translocation of NF κB in the neurons and the expression of IL 1, TNF α, and ICAM 1 in the brain. Western blotting was used to detect the expression of NF κB. The opposite non ischemic cortexes were used as controls. Results Two to 24 hours after the reperfusion NF κB was significantly translocated from the cytoplasm into the nucleus; however, NF κB remained in the cytoplasm of bilateral cortexes in the sham operation groups, and the nonischemic cortexes in the I/R and protofol groups. The traslocation of NF κB from cytoplasm into nucleus was significantly inhibited in the ischemic cortex of the propofol group. The expression values of NF κB in the nuclei of ischemic cortexes in the I/R group 2 to 24 hours after reperfusion were significantly higher than those in the sham operation group and the nonischemic cortexes of the I/R and propofol groups (all P <0.01). The expression values of NF κB in the ischemic cortex of the propofol group 2 to 24 hours after reperfusion was significantly lower than that of the I/R group (all P <0.05). The expression values of IL 1, TNF α, and ICAM 1 in the ischemic cortexes were significantly higher than that in the cortex of the sham operation group and those in the nonischemic cortexes of the I/R group and propofol group ( P <0.01 or P <0.05) and the expression values of IL 1, TNF α, and ICAM 1 in the propofol group were all significantly lower than those in the I/R group (all P <0.05). Conclusion Propofol inhibits the inflammatory reaction by inhibiting the NF κB activation during focal ischemia reperfusion which may be one of the mechanisms of its neuroprotective function.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2004年第24期2110-2114,共5页
National Medical Journal of China
