苦参碱对神经病理性大鼠背根神经节P2X3受体、疼痛行为学和疼痛阈值的影响

Effects of Matrine on P2X3 Receptor, Pain Behavior and Pain Threshold in Neuropathic Rat Dorsal Root Ganglion

目的:探讨苦参碱对神经病理性大鼠背根神经节P2X3受体、疼痛行为学和疼痛阈值的影响。方法:选择Sprague-Dawley雄性大鼠30只,随机分为3组,包括模型组、试验组和假手术组。于大鼠造模成功1 d后,试验组给予30 mg/(kgod)的剂量在腹腔注射苦参碱溶液,1次/d;给予假手术组和模型组腹腔注射等量浓度为0.9%的氯化钠溶液,1次/d,共14 d。进行自发疼痛行为学评分检测、机械痛阈值检测、热痛阈值检测、P2X2和P2X3mRNA相对表达量检测、P2X2和P2X3蛋白表达水平检测,以及氧化应激指标水平检测。结果:术后模型组与试验组自发性疼痛行为学评分与假手术组比均升高,自术后第5天起,与模型组比,试验组自发性疼痛行为学评分明显低于模型组(P<0.05);自术后第3天起,相较于假手术组,模型组机械痛阈值、热痛阈值显著下降,相较于模型组,试验组自术后第5天起机械痛阈值、热痛阈值显著上升(均P<0.05);术后第14天试验组与假手术组机械痛阈值、热痛阈值对比无差异(P>0.05);模型组P2X2和P2X3mRNA、P2X2及P2X3蛋白比假手术组和试验组高(均P<0.05),试验组和假手术组P2X2、P2X3mRNA、P2X2及P2X3蛋白比较无差异(P>0.05);干预前及干预1、2周后模型组大鼠脊髓组织SOD比假手术组低,MDA比假手术组高;试验组大鼠脊髓组织SOD比模型组高,MDA比模型组低(均P<0.05)。结论:苦参碱可有效缓解神经病理性痛的所引发的机械痛觉和热痛觉,镇痛作用较好,机制可能在于其可使大鼠背根神经元中P2X2、P2X3受体下降相关,同时其在抑制神经病理性大鼠脊髓组织氧化应激反应方面有一定的作用,与其在对神经病理性痛大鼠脊髓组织神经元凋亡的抑制有密切关系。

Objective:To investigate the effects of matrine on P2X3 receptor,pain behavior and pain threshold in neuropathic rat dorsal root ganglion.Methods:Thirty Sprague-Dawley male rats were randomly divided into 3 groups,including model group,experimental group and sham operation group.One day after successful modeling,the experimental group was given 30 mg/(kgod)intraperitoneal injection of matrine solution,once a day;Sham operation group and model group were given intraperitoneal injection of 0.9%sodium chloride solution once a day for 14 days.Spontaneous pain behavioral score,mechanical pain threshold,thermal pain threshold,P2X2 and P2X3mRNA relative expression levels,P2X2 and P2X3 protein expression levels,and oxidative stress index levels were detected.Results:The scores of spontaneous pain behavior in both the model group and the experimental group were higher than those in the sham operation group.Since the 5th day after surgery,the scores of spontaneous pain behavior in the experimental group were lower than those in the model group(P<0.05).Compared with the sham operation group,the mechanical pain threshold and thermal pain threshold in the model group were decreased from the 3rd day after surgery,while the mechanical pain threshold and thermal pain threshold in the experimental group were increased from the 5th day after surgery(all P<0.05).There were no differences in mechanical pain threshold and thermal pain threshold between experimental group and sham operation group on day 14 after surgery(P>0.05).P2X2 and P2X3 mrna,P2X2 and P2X3 proteins in model group were higher than those in sham operation group and experimental group(P<0.05),but there were no differences in P2X2,P2x3 mRNA,P2X2 and P2x3 proteins between experimental group and sham operation group(P>0.05).SOD and MDA of spinal cord in model group were lower and higher than those in sham group before intervention and 1 and 2 weeks after intervention.SOD and MDA of spinal cord tissue of experimental group were higher than those of model group(all P<0.05).Conclusion:Matrine can effectively relieve mechanical and thermal pain induced by neuropathic pain,and has good analgesic effect.The mechanism may be that matrine can reduce P2X2 and P2X3 receptors in dorsal root neurons of rats,and it also plays a role in inhibiting oxidative stress response of spinal cord tissue of neuropathic rats.It is closely related to the inhibition of neuronal apoptosis in spinal cord of neuropathic pain rats.