紫杉醇对海马神经元γ-氨基丁酸B型受体表达的影响及核因子-κB通路的调控作用
자삼순대해마신경원γ-안기정산B형수체표체적영향급핵인자-κB통로적조공작용
Effects of paclitaxel on γ-aminobutyric acid B receptors expression and nuclear factor-κB pathway regulation in hippocampal neurons
  • 万方数据
    中华实验外科杂志 중화실험외과잡지
    Chinese Journal of Experimental Surgery
    2015年 9期 2113-2116 ,共4页

    赵爽%李昭%王秀丽%刘飞飞%刘朋%郭跃先

    조상%리소%왕수려%류비비%류붕%곽약선

    紫杉醇%海马神经元%γ-氨基丁酸B型受体%p38丝裂原活化蛋白激酶%核因子-κB 紫杉醇%海馬神經元%γ-氨基丁痠B型受體%p38絲裂原活化蛋白激酶%覈因子-κB
    자삼순%해마신경원%γ-안기정산B형수체%p38사렬원활화단백격매%핵인자-κB
    Paclitaxel%Hippocampal neuron%γ-aminobutyric acid B receptors%p38 mitogen-activated protein kinase%Nuclear factor-κB
    目的 通过给予核因子-κB(NF-κB)抑制剂(SN50)及其上游通路p38丝裂原活化蛋白激酶(p38MAPKs)抑制剂(SB203580),观察紫杉醇对海马神经元γ-氨基丁酸B型受体(GABAB受体)表达影响及p38MAPKs/NF-κB通路在其中的调控作用.方法 选取原代培养5d、浓度为1 ×109/L的海马神经元随机分为6组:对照组(C组)、10 μmol/L SB203580处理组(SB组)、53 mg/LSN50处理组(SN组)、1μmol/L紫杉醇处理组(N组)、10 μmol/L SB203580+1μmol/L紫杉醇处理组(SB+N组)、53 mg/L SN50+1μmol/L紫杉醇处理组(SN +N组),培养时间为24 h,观察6组海马神经元形态学变化、早期凋亡率、NF-κB及GABAB受体蛋白表达变化.结果 与C组比较,N、SB +N和SN+N组海马神经元的轴突和树突分枝均有所减少,而SB组及SN组的神经元形态结构基本正常.N、SB +N和SN+N组的海马神经元GABAB受体表达与NF-κB蛋白表达及早期凋亡率变化一致:与C组比较,N、SB+N和SN +N组的NF-κB蛋白(N组:3.452±0.654;SB +N组:1.729±0.461;SN+N组:1.604±0.361)、早期凋亡率[N组:(49.16±3.12)％;SB +N组:(31.18±3.02)％;SN +N组:(28.47±3.75)％]及GABAB受体表达(N组:0.381 ±0.014;SB +N组:0.243 ±0.013;SN+ N:0.268 ±0.027)均明显增高(P＜0.05),SN组的NF-κB蛋白、早期凋亡率及GABAB受体表达则均显著降低(P＜0.05),而SB组的GABAB受体表达及早期凋亡率则无显著变化(P＞0.05);与N组比较,其余5组海马神经元NF-κB蛋白表达、早期凋亡率及GABAB受体均显著降低(P＜0.05),但与SB组或SN组比较,SB +N组与SN +N组NF-κB蛋白、早期凋亡率及GABAB受体表达的增高幅度明显减少(P＜0.05).而SB组与SN组,SB +N组与SN +N组比较,上述3项指标差异无统计学意义(P＞0.05).结论 紫杉醇可通过上调NF-κB蛋白诱发海马神经元凋亡及GABAB受体表达增多,阻断NF-κB通路可下调GABAB受体表达,以减缓紫杉醇引起的细胞凋亡等中枢神经毒性,NF-κB在其中发挥关键调控作用.
    목적 통과급여핵인자-κB(NF-κB)억제제(SN50)급기상유통로p38사렬원활화단백격매(p38MAPKs)억제제(SB203580),관찰자삼순대해마신경원γ-안기정산B형수체(GABAB수체)표체영향급p38MAPKs/NF-κB통로재기중적조공작용.방법 선취원대배양5d、농도위1 ×109/L적해마신경원수궤분위6조:대조조(C조)、10 μmol/L SB203580처리조(SB조)、53 mg/LSN50처리조(SN조)、1μmol/L자삼순처리조(N조)、10 μmol/L SB203580+1μmol/L자삼순처리조(SB+N조)、53 mg/L SN50+1μmol/L자삼순처리조(SN +N조),배양시간위24 h,관찰6조해마신경원형태학변화、조기조망솔、NF-κB급GABAB수체단백표체변화.결과 여C조비교,N、SB +N화SN+N조해마신경원적축돌화수돌분지균유소감소,이SB조급SN조적신경원형태결구기본정상.N、SB +N화SN+N조적해마신경원GABAB수체표체여NF-κB단백표체급조기조망솔변화일치:여C조비교,N、SB+N화SN +N조적NF-κB단백(N조:3.452±0.654;SB +N조:1.729±0.461;SN+N조:1.604±0.361)、조기조망솔[N조:(49.16±3.12)％;SB +N조:(31.18±3.02)％;SN +N조:(28.47±3.75)％]급GABAB수체표체(N조:0.381 ±0.014;SB +N조:0.243 ±0.013;SN+ N:0.268 ±0.027)균명현증고(P＜0.05),SN조적NF-κB단백、조기조망솔급GABAB수체표체칙균현저강저(P＜0.05),이SB조적GABAB수체표체급조기조망솔칙무현저변화(P＞0.05);여N조비교,기여5조해마신경원NF-κB단백표체、조기조망솔급GABAB수체균현저강저(P＜0.05),단여SB조혹SN조비교,SB +N조여SN +N조NF-κB단백、조기조망솔급GABAB수체표체적증고폭도명현감소(P＜0.05).이SB조여SN조,SB +N조여SN +N조비교,상술3항지표차이무통계학의의(P＞0.05).결론 자삼순가통과상조NF-κB단백유발해마신경원조망급GABAB수체표체증다,조단NF-κB통로가하조GABAB수체표체,이감완자삼순인기적세포조망등중추신경독성,NF-κB재기중발휘관건조공작용.
    Objective To investigate the effects of paclitaxel on γ-aminobutyric acid B (GABAs) receptors expression and p38 mitogen-activated protein kinase (p38MAPK)/nuclear factor-κB (NF-κB) pathway in the hippocampal neurons regulated by giving NF-κB inhibitor (SN50) and p38MAPK inhibitor (SB203580).Methods The primary cultured hippocampal neurons which had been cultivated for 5 days in vitro were randomly selected,and the density was about 1 × 109/L.These neurons were randomly divided into six groups:control group (C group),10 μmol/L SB203580 group (SB group),53 mg/L SN50 group (SN group),1 μmol/L paclitaxel group (N group),10 μmol/L SB203580 + l0 μmol/L paclitaxel group (SB + N group),and 53 mg/L SN50 + 10 μmol/L paclitaxel group (SN + N group).All of the hippocampal neurons were cultured for 24 h.Morphologic changes,the early apoptosis rate,and expression of GABAB receptors and NF-κB in hippocampal neurons were observed in six groups.Results As compared with C group,the axons and dendrites of hippocampal neurons in N group,SB + N group and SN + N group were decreased,while the morphology and structure of neurons in SB group and SN group were normal.The expression of GABAB receptors and NF-κB protein and early poptnsis rate in hippocampal neurons of N group,SB + N group and SN + N group were consistent.As compared with C group,the expression of GABAB receptors (N:0.381 ± 0.014;SB + N:0.243 ± 0.013;SN + N:0.268 ± 0.027),early apoptosis rate [N:(49.16 ± 3.12) ％;SB + N:(31.18 ± 3.02) ％;SN + N:(28.47 ± 3.75)％] and NF-κB protein (N:3.452 ±0.654;SB +N:1.729 ±0.461;SN +N:1.604 ±0.361) were significantly up-regulated in N group,SB + N group and SN + N group (P ＜ 0.05),while the expression of GABAB receptors,early apoptosis rate and NF-κB protein were down-regulated in SN group (P ＜ 0.05),and the expression of GABAB receptors and early apoptosis rate had no significant changes in SB group (P ＞ 0.05).As compared with N group,the expression of GABAB receptors,early apoptosis rate and NF-κB protein were down-regulated in the other five groups of hippocampus neurons (P ＜ 0.05),but as compared with SB group or SN group,the increases in the expression of GABAB receptors,early apoptosis rate and NF-κB protein were significantly reduced (P ＜ 0.05).There was no significant difference between SB group and SN group,as well as between SB + N group and SN + N group (P ＞ 0.05).Conclusion Paclitaxel can induce apoptosis of hippocampal neurons and increase GABAB receptors expression by up-regulating NF-κB protein,and the inhibition of NF-κB pathway can down-regulate the expression of GABAB receptors to slow the central neurotoxicity induced by paclitaxel,in which NF-κB may play a key regulatory role.
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