氧化苦参碱的镇痛作用对钙通道和γ-氨基丁酸的影响  

The Analgesia of Oxymatrine Affecting Calcium Channel and GABA Release

作　　者：吕晓强[1,2] 杨丽[1,2] 邓扬鸥[3] 吴世星 刘永刚[4] 

机构地区：[1]辽宁中医药大学基础医学院药理教研室 [2]辽宁中医药大学省部共建中医脏象理论及应用教育部重点实验室,沈阳110847 [3]中国医科大学附属第一医院干诊科,沈阳110001 [4]武警广东省总队医院药剂科,广州510507

出　　处：《中国中西医结合杂志》2015年第5期603-607,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金(青年科学基金)资助项目(No.81102901);教育部留学回国人员科研启动基金(教外司留[2012]940号);辽宁省自然科学基金资助项目(No.201102151)

摘　　要：目的通过建立神经病理性疼痛模型,观察氧化苦参碱(oxymatrine,OMT)的镇痛作用,探讨OMT的镇痛作用与高电压依赖性钙通道(high voltage-dependent calcium channels,HVDCCs)mRNA表达及与γ-氨基丁酸(GABA)含量变化的关系。方法 C57 BL/6小鼠共66只,随机分成假手术组、模型组、OMT组,每组22只。建立部分坐骨神经结扎神经病理性疼痛模型,采用up and down方法测定小鼠足底机械缩足反应阈值(MWT);利用实时荧光定量PCR(real-time PCR)方法分别检测脑、脊髓组织中各HVDCCs mRNA的表达;使用ELISA试剂盒测定脑、脊髓组织中GABA含量。结果与0天比较,模型组第7、10、14天结扎侧左后足MWT降低(P<0.05);与假手术组比较,模型组小鼠第7天结扎侧左后足MWT显著降低(P<0.05);与0天比较,OMT组术后第7天给药前MWT降低(P<0.05),给药后MWT则升高(P<0.05)。与假手术组比较,模型组脑组织中Cav1.2、Cav1.3、Cav2.1及Cav2.3 mRNA水平明显升高,Cav2.2 mRNA明显降低(P<0.05),而脊髓组织中Cav1.2、Cav1.3 mRNA水平明显升高,Cav2.1、Cav2.2、Cav2.3 mRNA明显降低(P<0.05);与模型组比较,OMT组脑组织中Cav1.2、Cav1.3、Cav2.1及Cav2.3 mRNA水平明显降低,Cav2.2 mRNA明显升高(P<0.05),而脊髓组织中Cav1.3 mRNA水平明显降低,Cav2.1、Cav2.2、Cav2.3 mRNA明显升高(P<0.05)。与假手术组比较,模型组脑组织中GABA含量下降(P<0.05);与模型组比较,OMT组脑组织中GABA含量升高(P<0.05);在脊髓组织中,各组GABA的含量变化比较,差异无统计学意义(P>0.05)。结论氧化苦参碱对神经病理性疼痛有抑制作用,其镇痛作用可能与HVDDCs有关,其中Cav2.2可能直接影响GABA神经递质的释放。Objective To explore the analgesia of oxymatrine （OMT） affecting high voltage-de- pendent calcium channels （HVDCCs） and GABA release under neuropathic pain condition. Methods To- tally 66 C^TBL/6 mice were randomly divided into the sham-operation group, the model group, and the OMT group, 22 in each group. Neuropathic pain models were established by partial sciatic nerve ligation （PSNL）. Hind paw plantar mechanical response threshold （MWT） was measured by up-and-down method with Von-Frey filament, mRNA expression of HVDCCs in brains and spinal cords was detected with Realtime PCR and concentration of GABA was determined using ELISA kit. Results Compared with day 0,the left hind paw MWT was decreased on day 7,10, and 14 in the model group （P 〈0.05）. Compared with the sham-operation group, the left hind paw MWT was significantly reduced in the model group on day 7 （P 〈0.05）. The MWT of PSNL ipsilateral hind paw was decreased on day 7 before OMT administration, when compared with day 0 （P 〈0.05）, and increased after OMT administration （P 〈0.05）. Compared with the sham-operation group, mRNA levels of Cavl. 2, Cavl. 3, Cav2.1, and Cav2.3 in brain tissues were increased and those of Cav2.2 were decreased significantly in the model group （P 〈0.05）. In spinal cord tissues, mRNA levels of Cavl. 2 and Cavl. 3 were increased, but those of Cav2.1, Cav2.2, and Cav2.3 were decreased significantly in the model group, when compared with those of the sham-opera- tion group （P 〈0.05）. Compared with the model group, mRNA levels of Cavl. 2, Cavl. 3, Cav2.1, and Cav2.3 in brain tissues were decreased, and those of Cav2.2 were increased significantly in the OMT group （P 〈0.05）. In spinal cord tissues of the OMT group, mRNA levels of Cavl. 3 decreased and those of Cav2.1, Cav2.2, and Cav2.3 increased significantly with statistical difference, when compared with those of the model group （P 〈0.05）. Compared with the sham-operation group, GABA levels in brain tissues decrease

关 键 词：氧化苦参碱 神经病理性疼痛 钙通道 Γ-氨基丁酸 

分 类 号：R285.5[医药卫生—中药学]