[Effect of propofol on the activation of nuclear factor-kappa B and expression of inflammatory cytokines in cerebral cortex during transient focal cerebral ischemia-reperfusion: experiment with rats].
OBJECTIVE
To investigate the effect of propofol on the activation of nuclear factor-kappa B (NF-kappa B) and the expression of inflammatory cytokines, such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), 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-kappaB in the neurons and the expression of IL-1, TNF-alpha, and ICAM-1 in the brain. Western blotting was used to detect the expression of NF-kappa B. The opposite non-ischemic cortexes were used as controls.


RESULTS
Two to 24 hours after the reperfusion NF-kappaB was significantly translocated from the cytoplasm into the nucleus; however, NF-kappa B remained in the cytoplasm of bilateral cortexes in the sham operation groups, and the nonischemic cortexes in the I/R and protofol groups. The translocation of NF-kappa B from cytoplasm into nucleus was significantly inhibited in the ischemic cortex of the propofol group. The expression values of NF-kappa B 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-kappa B 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-alpha, 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-alpha, and ICAM-1 in the propofol group were all significantly lower than those in the I/R group (all P < 0.05).


CONCLUSIONS
Propofol inhibits the inflammatory reaction by inhibiting the NF-kappa B activation during focal ischemia-reperfusion which may be one of the mechanisms of its neuroprotective function.
Feng
Chun-sheng
CS
Department of Anesthesiology, Beijing Chaoyang Hospital Affiliated to Capital University of Medical Sciences, Beijing 100020, China.
Ma
Hai-chun
HC
Yue
Yun
Y
Zhang
Yong-qian
YQ
Qu
Xiang-dong
XD
D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D007375:Interleukin-1; D016328:NF-kappa B; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D015742:Propofol