孕酮通过NF-κB调控脑损伤后大鼠海马神经元COX-2的表达

Progesterone influence COX-2 expression on hippocampal neurons after traumatic brain injury in rats by NF-κB signaling pathway

目的:研究NF-κB对脑损伤大鼠海马神经元环氧合酶-2(COX-2)的表达调控作用,探讨孕酮(PROG)对脑损伤(TBI)后大鼠海马神经元保护作用及其可能机制.方法:雄性SD大鼠45只随机分为假手术组、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,用Nissl染色法、免疫组织化学法及免疫蛋白印记法,观察大鼠海马CA1区NF-κB,COX-2以及前列腺素E2(PGE2)的表达变化;并观察孕酮对上述指标的影响.结果:与假手术组大鼠相比,损伤组大鼠海马CA1区NF-κB(24.0±2.5),COX-2(35.9±2.7),PGE2(34.4±2.9)阳性神经元的数量较假手术组NF-κB(1.9±0.9),COX-2(1.5±0.7),PGE2(1.7±0.7)显著增加(P<0.05);PROG治疗组与损伤组比较,海马CA1区NF-κB(14.2±1.8),COX-2(16.6±2.7),PGE2(16.5±2.0)阳性神经元的数量明显减少(P<0.05).结论:NF-κB对脑损伤后海马神经元COX-2表达起调控作用;PROG可能通过影响NF-κB而调控COX-2的表达,对大鼠海马神经元起保护作用.

AIM：To investigate the effect of progesterone （PROG） on the expression of nuclear factor-κB （NF-κB） and cyclooxygenase-2 （COX-2） in hippocampal neurons after traumatic brain injury （TBI） in rats. METHODS：Forty-five male Spraque-Dawley rats 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. Nissl staining,immunohistochemistry and Western blot for NF-κB,COX-2 and prostaglandin E2 （PGE2） was used to observe the changes of positive cell number and protein level in hippocampal neurons and their changes after treated with PROG. RESULTS ： The number of NF-KB （24.0 ± 2.5）, COX-2 （35.9±2.7）, PGE2 （34.4 ±2.9） immunoreactive neurons significantly increased in hippocampal at 24 h after TBI compared with the number of NF-KB （ 1.9 ± 0.9） , COX-2 （ 1.5 ± 0.7 ） , PGE2 （ 1.7±0.7 ） immunoreactive neurons in sham group. In treatment with PROG, the number of NF-KB （14.2±1.8）, COX-2 （16.6±2.7）, PGE2 （16.5 ±2.0） immunoreactive neurons was reduced obviously as compared with the TBI group （P 〈 0.05）. CONCLUSION： NF-KB may play an important role in mediating COX-2 expression in hippocampal neurons after traumatic brain injury in rats, and progesterone may influence the expression of NF-KB and protect the hippocampal neurons.