摘要目的 评价大鼠神经病理性痛时背根神经节硫化氢(H2S)与P2X3受体的关系.方法 取鞘内置管成功的SPF级健康雄性SD大鼠36只,体重180～200 g,4～6周龄,采用随机数字表法分为3组(n=12):假手术组(S组)、神经病理性痛组(NP组)和内源性H2S合成酶[胱硫醚-β-合成酶(CBS)]抑制剂氨基氧乙酸(AOAA)组(A组).鞘内置管成功后第3天,采用坐骨神经缩窄性损伤(CCI)法制备神经病理性痛模型.CCI后1d,A组鞘内注射AOAA(10 μg/kg) 10μl+生理盐水10μl,S组和NP组鞘内注射生理盐水20μl,连续14 d(1次/d).于CCI前1d、CCI后1、3、7、10和14 d鞘内给药后30 min时测定热缩足潜伏期和机械缩足反应阈.于CCI后7和14 d时处死大鼠,取术侧L4-6背根神经节组织,采用Western blot法检测CBS及P2X3受体的表达.结果 与S组比较,NP组CCI后各时点热缩足潜伏期缩短,机械缩足反应阈降低,背根神经节CBS及P2X3受体表达上调(P＜0.05);与NP组比较,A组CCI后各时点热缩足潜伏期延长,机械缩足反应阈升高,背根神经节CBS及P2X3受体表达下调(P＜0.05).结论 背根神经节H2S可上调P2X3受体表达,该作用可能参与了大鼠神经病理性痛的病理生理机制.

abstractsObjective To evaluate the relationship between hydrogen sulfide (H2S) and P2X3 receptors in dorsal root ganglions (DRGs) of rats with neuropathic pain (NP).Methods Thirty-six healthy male Sprague-Dawley rats,aged 4-6 weeks,weighing 180-200 g,in which IT catheters were successfully implanted,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),group NP and endogenous H2S synthase (cystathionine beta-syntheses [CBS]) inhibitor animooxyacetic acid (AOAA) group (group A).NP was induced by chronic constriction injury (CCI) to the sciatic nerve at 3 days after IT catheters were successfully implanted.AOAA (10 μg/kg) 10 μl and normal saline 10 μl were intrathecally injected once a day for 14 consecutive days starting from 1 day after CCI in group A,and normal saline 20 μl was intrathecally injected instead in S and NP groups.At 1 day before CCI and 1,3,7,10 and 14 days after CCI,the thermal paw withdrawal latency (TWL) and mechanical paw withdrawal threshold (MWT) were measured at 30 min after intrathecal injection.The animals were sacrificed at 7 and 14 days after CCI,and ipsilateral DRGs of the lumbar segment (L4-6) were removed for detection of the expression of CBS and P2X3 receptors by Western blot.Results Compared with group S,the TWL was significantly shortened,MWT was decreased,and the expression of CBS and P2X3 receptors in DRGs was up-regulated at each time point after CCI in group NP (P＜0.05).Compared with group NP,the TWL was significantly prolonged,the MWT was increased,and the expression of CBS and P2X3 receptors in DRG s was down-regulated at each time point after CCI in group A (P＜0.05).Conclusion H2S in DRG s can up-regulate the expression of P2X3 receptors,which may be involved in the pathophysiological mechanism of NP in rats.