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目的:通过观察氧化苦参碱(oxymatrine,OMT)对神经病理性疼痛小鼠的脑、脊髓、背根神经结(DRG)的高电压依赖性钙通道(high voltage-dependent calcium channels,HVDCCs)辅助亚基mRNA表达量的影响,探讨氧化苦参碱的镇痛作用相关机制。方法:将15只C57BL/6小鼠随机分成假手术组、模型组、氧化苦参碱组,每组5只,通过部分结扎小鼠左右两侧后腿坐骨神经建立神经病理性疼痛模型,应用实时荧光定量PCR(real-time PCR)检测脑、脊髓、背根神经节(DRG)3个组织中高电压依赖性钙通道多种辅助亚基mRNA表达情况。结果:在脑组织中,模型组小鼠辅助亚基α2δ1、α2δ2的mRNA水平明显升高,α2δ3、α2δ4的mRNA水平明显降低。与模型组比较,氧化苦参碱组中α2δ1、α2δ2及γ1的mRNA水平明显著降低,α2δ4的mRNA水平明显升高。在脊髓组织中,模型组小鼠的α2δ1、α2δ2、α2δ3、γ1及γ4的mRNA水平均明显升高;氧化苦参碱(150mg/kg)处理使得其中模型组升高的α2δ1、α2δ2、α2δ3的mRNA水平显著降低。在DRG组织中,模型组小鼠α2δ1的mRNA水平明显升高,α2δ2、α2δ3的mRNA水平明显降低;氧化苦参碱(150mg/kg)处理使得其中模型组升高的α2δ1的mRNA水平明显降低。α2δ4、γ3在DRG组织中未见表达。各组织中,部分坐骨神经结扎及氧化苦参碱给药对其余β、γ等亚基的mRNA表达水平变化影响无统计学意义。结论:氧化苦参碱的镇痛作用与高电压依赖性钙通道辅助亚基α2δ1有高度相关性。
OBJECTIVE: To observe the effect of oxymatrine (OMT) on high voltage-dependent calcium channels (HVDCCs) in brain, spinal cord and dorsal root ganglion (DRG) of neuropathic pain mice Based mRNA expression of the impact of oxymatrine analgesic effect of the relevant mechanisms. Methods: Fifteen C57BL / 6 mice were randomly divided into sham operation group, model group and oxymatrine group, with 5 rats in each group. The neuropathic pain model was established by partial ligation of the sciatic nerve of the left and right hind legs of the mice. Real - time fluorescence Quantitative PCR (real-time PCR) was used to detect mRNA expression of multiple helper subunits of high voltage-dependent calcium channels in brain, spinal cord and dorsal root ganglion (DRG). Results: In the brain tissue, the mRNA levels of the auxiliary subunits α2δ1 and α2δ2 in the model group were significantly increased, while the mRNA levels of α2δ3 and α2δ4 in the model group were significantly decreased. Compared with the model group, mRNA levels of α2δ1, α2δ2 and γ1 in oxymatrine group were significantly decreased, α2δ4 mRNA levels were significantly increased. In the spinal cord tissue, the mRNA levels of α2δ1, α2δ2, α2δ3, γ1 and γ4 in the model group were significantly increased; the treatment with 150mg / kg oxymatrine increased the expression of α2δ1, α2δ2 and α2δ3 mRNA levels significantly reduced. In DRG, the mRNA level of α2δ1 was significantly increased and the mRNA levels of α2δ2 and α2δ3 were significantly decreased in model group. Oxymatrine (150mg / kg) significantly decreased the mRNA level of α2δ1 in model group. α2δ4, γ3 no expression in the DRG tissue. In each group, some sciatic nerve ligation and oxymatrine administration had no significant effect on the changes of mRNA expression level of other β, γ and other subunits. Conclusion: The analgesic effect of oxymatrine is highly correlated with α2δ1, a subunit of high voltage-dependent calcium channel.