摘要
目的:观察巴氯芬干预前后GABAA受体γ2亚基在坐骨神经压榨性损伤(Chronic ConstrictionInjury,CCI)模型大鼠背根神经节(Dorsal Root Ganglion,DRG)神经元上的功能和表达变化.方法:制备CCI模型,热板实验检测热刺激缩足反射潜伏期(Thermal Withdrawal Latency,TWL);以灌胃的方式给予CCI模型鼠巴氯芬干预14天,取大鼠L4~L6 DRG神经元进行膜片钳实验,观测巴氯芬干预前后CCI模型鼠DRG神经元GABA介导的内向电流变化;应用Western blot技术检测巴氯芬干预前后CCI模型鼠GABAA受体γ2亚基的表达变化.结果:(1) CCI模型大鼠的TWL比正常组明显缩短,巴氯芬干预组模型大鼠的TWL较CCI模型组明显延长(P<0.05);(2)巴氯芬抑制CCI模型大鼠D RG神经元GABA介导的内向电流(P<0.05); (3) CCI手术侧和手术对侧DRG神经元上GABAA受体γ2亚基的表达量下调(P<0.05),但是磷酸化γ2亚基表达量上调(P<0.05);巴氯芬干预后的GABAA受体γ2亚基表达量较CCI组下调,磷酸化的γ2亚基表达量较CCI组上调.结论:神经病理性痛状态下,GABAA受体γ2亚基发生磷酸化可能是GABA介导的突触前抑制作用减弱的原因之一,而巴氯芬可能通过磷酸化GABAA受体γ2亚基抑制GABAA受体功能.
Objective: To investigate the expression of GABAA receptor y z subunit on DRG (Dorsal Root ganglion) neurons of CCI (Chronic Constriction Injury) model rats after baclofen intervention. Methods: Hotplate experiment was used to detect the change of thermal withdrawal latency (TWL) before and after baclofen intervention in CCI model rats. After baclofen intragastric administration for 14 days in CCI rats whole-cell patch clamp recording technique was used to clarify the change of GABA-mediated inward currents in L4- L6 DRG neurons. Western blot technique was used to study the expression of GABAA receptor y subunit in DRG neurons. Results: (1) TWL were increased apparently in baclofen interventioned CCI model rats compared with CCI group (P 〈 0.05). (2) Whole-cell patch clamp recording technique showed that baclofen inhibited GABA-mediated inward currents in CCI model rats (P 〈 0.05). (3) The expression of GABAA receptor γ 2 subunit reduced in both ipsilateral side and contralateral side in CCI model rats (P 〈 0.05), but the phosphorylation of γ2 subunit increased (P 〈 0.05). GABAA receptor γ2 subunit significantly reduced and the phosphorylation of γ2 subunit increased after baclofen intervention. Conclusion: Under the neuropathicpain condition, because of the phosphorylation of GABAA receptor γ2 subunit, GABA's presynaptic inhibition effect is reduced in primary sensory afferent terminals, and baclofen may inhibit the function of GABAA receptor via phosphorylating GABAA receptor γ2 subunit.
出处
《中国疼痛医学杂志》
CAS
CSCD
北大核心
2014年第12期866-870,共5页
Chinese Journal of Pain Medicine
基金
GABA介导的初级感觉传入突触前抑制在神经病理性疼痛中去抑制的机制研究*兵团优秀青年创新基金专项(2010JC33)