【摘要】 目的:研究孕酮(progesterone,PROG)对大鼠脑损伤后皮质COX-2、iNOS、NF-κB和caspase-3表达的影响,以探讨PROG脑保护作用的可能机制。方法:雄性SD大鼠45只,随机分为假手术组、脑损伤组和PROG治疗组,按照改良的Feeney自由落体损伤装置制作大鼠脑损伤模型。PROG治疗组伤后1,6h腹腔注射PROG16mg/kg,各组于伤后24h取材。用免疫组织化学法及免疫蛋白印迹法,观察大鼠皮质COX-2、iNOS、NF-κB和caspase-3的免疫阳性细胞数和蛋白表达水平变化。结果:与假手术组大鼠相比,脑损伤组大鼠皮质COX-2、iN-OS、NF-κB和caspase-3阳性细胞数和蛋白表达水平较假手术组COX-2、iNOS、NF-κB和caspase-3显著增加(P<0.05);PROG治疗组与脑损伤组比较,大鼠皮质COX-2、iNOS、NF-κB和caspase-3阳性细胞数和蛋白表达水平明显减少(P<0.05)。结论:PROG可通过抑制NF-κB的活化,阻断NF-κB和iNOS自身强化的炎症反应过程,降低COX-2、caspase-3的表达,抑制脑损伤后的炎症反应和细胞凋亡,从而发挥脑保护作用。更多还原

【Abstract】 Objective:To investigate the effect of progesterone(PROG) on the expression of COX-2、iNOS、NF-κB and caspase-3 in the cortex after traumatic brain injury (TBI) in rats.To study on the neuroprotective effects and molecular mechanism of progesterone on TBI.Methods:Male Spraque-Dawley rats (n=45) were randomly divided into 3 groups:sham-operated group (n=15),TBI group (n=15) and PROG-treated group (n=15).The rat model of TBI was duplicated with the improved Feeney’s method.The progesterone in the PROG-treated group were injected into peritoneal cavity at 1 h and 6 h after the injury.The rats were killed respectively in three groups at 24 h after injury.The changes of the positive cellular numbers and protein level of COX-2,iNOS,NF-κB and caspase-3 in the cortex were examined by immunohistochemistry and Western Blot.Results:The positive cellular numbers and protein level of COX-2,iNOS,NF-κB and caspase-3 in the cortex of the TBI group were distinctly higher than those of sham-operated the group (P<0.05).The positive cellular numbers and protein level of COX-2,iNOS,NF-κB and caspase-3 in the cortex of the PROG-treated group were distinctly less than those of the TBI group(P<0.05).Conclusion:PROG had protective effect on TBI that may relate to inhibition of NF-κB activity,block of the cascade reaction NF-κB and iNOS,down-regutation the expression of COX-2 and caspase-3,and inhibition of inflammatory reaction and apoptosis after traumatic brain injury in rats.更多还原