基于GABA通路研究川芎素对神经病理性痛大鼠模型的保护作用  

Protective effect of ligustrazine on neuropathic pain in rats based on GABA pathway

作　　者：敬晓鹏[1] 保森竹[2] JING Xiaopeng;BAO Senzhu(Department of Pain,Affiliated Hospital of Qinghai University,Qinghai 810000,China;Plastic Surgery,Affiliated Hospital of Qinghai University)

机构地区：[1]青海大学附属医院疼痛科,青海810000 [2]青海大学附属医院整形外科

出　　处：《山西医科大学学报》2019年第6期734-739,共6页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(81560200)

摘　　要：目的探究基于γ-氨基丁酸(GABA)通路川芎素对神经病理性痛(NP)大鼠模型的保护作用。方法采用慢性坐骨神经压迫损伤法制备神经病理性痛大鼠模型。取健康SD雄性大鼠40只,随机分为5组:假手术组、慢性坐骨神经压迫损伤组(CCI组)、川芎素低、中、高剂量治疗组(50,100,200mg/kg),每组8只。假手术组和CCI组腹腔注射等体积的0.9%生理盐水。各组大鼠均于造模后第8天开始给药,连续7d。采用VonFreytest触觉测量套件(机械刺痛)、热刺痛仪及冷热板测痛仪分别于造模前1d,造模后7d,给药后1,3,5,7d测定各组大鼠坐骨神经机械刺激缩足反射阈值、热缩足反射潜伏期以及冷缩足反射阈值;在末次给药后24h采用qRT-PCR检测脊髓组织中GABA、GAD、GAT1mRNA表达,采用免疫印迹法(WB)检测脊髓组织中GABA、GAD、GAT1蛋白表达。结果与假手术组比,CCI模型组和川芎素各治疗组在造模后7d,给药后1,3,5,7d时大鼠机械缩足反射阈值显著降低(P<0.05),热缩足反射潜伏期显著降低(P<0.05),冷缩足反射阈值显著升高(P<0.05);与CCI模型组比,川芎素50,100,200mg/kg组在造模后7d,给药后1,3,5,7d时大鼠机械缩足反射阈值显著升高(P<0.05),热缩足反射潜伏期显著延长(P<0.05),冷缩足反射阈值显著降低(P<0.05);与假手术组、CCI模型组比较,川芎素50,100,200mg/kg组大鼠脊髓组织GABA、GADmRNA表达显著上调(P<0.05),GAT1mRNA显著下调(P<0.05);与假手术组、CCI模型组比较,川芎素200mg/kg组GABA、GAD蛋白表达水平显著上调,GAT1蛋白表达水平显著下调(P<0.05)。结论川芎素对慢性坐骨神经压迫损伤神经病理性痛有良好的镇痛作用,其机制可能与上调GABA通路中GABA、GAD表达和下调GAT1表达相关。Objective To explore the protective effect of ligustrazine on neuropathic pain(NP)rat model based onγ-aminobutyric acid(GABA)pathway.Methods The rat model of neuropathic pain was established by chronic sciatic nerve compression injury method.Forty healthy SD male rats were randomly divided into five groups:sham operation group,chronic sciatic nerve compression injury group(CCI group),ligustrazine low,medium and high dose treatment groups(50,100,200 mg/kg),with eight rats in each group.The rats in sham operation group and CCI group were injected with 0.9%saline of equal volume,and the rats in each group were given medicine on the 8th day after the establishment of the model for 7 consecutive days.Von Frey test tactile measurement kit(mechanical prick),hot prick pain meter and cold and hot plate pain meter were used to measure the foot reflex threshold of mechanical stimulation of sciatic nerve,latency of thermal foot reflex and cold foot reflex threshold of rats in each group one day before modeling,7 d after modeling and 1,3,5 and 7 d after administration respectively.At 24 h after the last administration,the mRNA expression of GABA,GAD and GAT1 in spinal cord tissue was detected by qRT-PCR,and the protein expression levels of GABA,GAD and GAT1 in spinal cord tissue were detected by immunoblotting(WB).Results Compared with sham operation group,the mechanical foot reflex threshold of rats in CCI model group and ligustrazine treatment groups significantly decreased at 7 d after modeling and 1,3,5 and 7 d after administration(P<0.05),the heat shrinking thermal withdrawal latency significantly decreased(P<0.05),and the cold shrinking reflex threshold significantly increased(P<0.05).Compared with CCI model group,the mechanical foot reflex threshold of rats in ligustrazine 50,100 and 200 mg/kg groups significantly prolonged at 7 d after modeling and 1,3,5 and 7 d after administration(P<0.05),the heat shrinking thermal withdrawal latency significantly increased(P<0.05),and the cold shrinking reflex threshold signi-fica

关 键 词：γ-氨基丁酸通路 川芎素 神经病理性痛 大鼠 

分 类 号：R741.02[医药卫生—神经病学与精神病学]