CAJ | 학술논문

目的研究帕瑞昔布钠对痫性发作大鼠海马神经元凋亡及B细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、caspase-3蛋白表达的影响. 方法 30只SD大鼠采用数字随机表法分为3组(n=10):帕瑞昔布钠组和致痫组大鼠分别以4 mg/kg帕瑞昔布钠和等体积生理盐水腹腔注射处理3d后,腹腔注射3 mmoL/kg新鲜配制的氯化锂,20 h后腹腔注射30 mg/kg盐酸匹罗卡品;对照组予腹腔注射与4 mg/kg帕瑞昔布钠等体积的生理盐水,不造模.观察3组大鼠行为学变化;造模7d后取材,TUNEL染色评价神经元凋亡情况;Western blotting检测Bcl-2、Bax和caspase-3蛋白表达水平. 结果所有致痫大鼠均非常易激惹,帕瑞昔布钠组自发性痫性发作(SRS)次数比致痫组明显减少,差异有统计学意义(P＜0.05).与对照组比较,致痫组大鼠海马Bcl-2、Bax、caspase-3表达水平增加,Bcl-2/Bax比值升高,差异有统计学意义(P＜0.05).与致痫组比较,帕瑞昔布钠组大鼠海马Bcl-2、Bax、caspase-3表达水平降低,Bcl-2/Bax比值降低,差异有统计学意义(P＜0.05).与对照组比较,帕瑞昔布钠组及致痫组大鼠海马TUNEL阳性细胞数均增多,差异有统计学意义(P＜0.05);与致痫组比较,帕瑞昔布钠组大鼠海马TUNEL阳性细胞数降低,差异有统计学意义(P＜0.05). 结论帕瑞昔布钠能减少海马神经元凋亡,抑制Bax、caspase-3蛋白的表达,影响Bcl-2蛋白的表达,其机制可能与帕瑞昔布钠作用于Bcl-2/Bax和caspase-3凋亡通路相关.
목적 연구파서석포납대간성발작대서해마신경원조망급B세포림파류/백혈병-2(Bcl-2)、Bcl-2상관X단백(Bax)、caspase-3단백표체적영향. 방법 30지SD대서채용수자수궤표법분위3조(n=10):파서석포납조화치간조대서분별이4 mg/kg파서석포납화등체적생리염수복강주사처리3d후,복강주사3 mmoL/kg신선배제적록화리,20 h후복강주사30 mg/kg염산필라잡품;대조조여복강주사여4 mg/kg파서석포납등체적적생리염수,불조모.관찰3조대서행위학변화;조모7d후취재,TUNEL염색평개신경원조망정황;Western blotting검측Bcl-2、Bax화caspase-3단백표체수평. 결과 소유치간대서균비상역격야,파서석포납조자발성간성발작(SRS)차수비치간조명현감소,차이유통계학의의(P＜0.05).여대조조비교,치간조대서해마Bcl-2、Bax、caspase-3표체수평증가,Bcl-2/Bax비치승고,차이유통계학의의(P＜0.05).여치간조비교,파서석포납조대서해마Bcl-2、Bax、caspase-3표체수평강저,Bcl-2/Bax비치강저,차이유통계학의의(P＜0.05).여대조조비교,파서석포납조급치간조대서해마TUNEL양성세포수균증다,차이유통계학의의(P＜0.05);여치간조비교,파서석포납조대서해마TUNEL양성세포수강저,차이유통계학의의(P＜0.05). 결론 파서석포납능감소해마신경원조망,억제Bax、caspase-3단백적표체,영향Bcl-2단백적표체,기궤제가능여파서석포납작용우Bcl-2/Bax화caspase-3조망통로상관.
Objective To research the effect ofparecoxib on hippocampal nerve cell apoptosis and expressions of B cell lymphoma/lewkmia-2 (Bcl-2),Bcl-2 associated X protein (Bax) and caspase-3 of epilepsy rats.Methods Thirty SD male rats were randomly divided into three groups (n=10):control group,parecoxib treatment group and epilepsy group.The rats in the parecoxib treatment group and epilepsy group were injected with 4 mg/kg of parecoxib and same volume of saline,respectively,and 3 d after that,they both were injected intraperitoneally with 3 mmol/kg of lithium chloride,and then,20 h after that,they were injected intraperitoneally with 30 mg/kg ofhydrochloride pilocarpine; while rats in the control group were only injected intraperitoneally with the same volume of saline.The behavior changes of rats in the three groups were observed.After 7 d,terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to evaluate the neuronal apoptosis and Western blotting was employed to evaluate the expressions of Bcl-2,Bax and caspase-3 in the hippocarnpus of all groups.Results All epilepsy rats were very irritable; spontaneous seizures (SRS) times of precoxib treatment group were significantly reduced as compared with those of epilepsy group (P＜0.05).As compared with those in the control group,the Bcl-2,Bax and caspase-3 expressions and Bcl-2/Bax ratio in the epilepsy group were increased with statistically significant differences (P＜0.05); As compared with those in the epilepsy group,the Bcl-2,Bax and caspase-3 expressions and Bcl-2/Bax ratio in the precoxib treatment group were decreased with statistically significant differences (P＜0.05).As compared with that in the control group,the number of TUNEL positive cells in hippocampus of rats in the precoxib treatment group and epilepsy group were significantly increased (P＜0.05); as compared with that in the epilepsy group,the number of TUNEL positive cells in the hippocampus of precoxib treatment group was statistically reduced (P＜0.05).Conclusion Parecoxib can reduce the apoptosis of hippocampus neurons through inhibiting the protein expressions of Bax and caspase-3 to affect the Bcl-2 protein expression,whose mechanism may be related to the pathways of Bcl-2/Bax and Caspase-3 proteins.