摘要
目的观察鞘内注射大麻素CB2受体激动剂AM1241对慢性坐骨神经结扎(CCI)大鼠机械痛阈、脊髓背角P2X4、P2Y12和P2Y13受体表达变化的影响。方法健康成年雄性Sprague-Dawley大鼠40只随机分为5组(n=8):假手术组、CCI组(坐骨神经结扎+鞘内注射0.005%DMSO生理盐水)、1 pmol/LAM1241处理组(坐骨神经结扎+鞘内注射AM1241 1pmol/L)、10 pmol/LAM1241处理组(坐骨神经结扎+鞘内注射AM1241 10 pmol/L)、100 pmol/LAM1241处理组(坐骨神经结扎+鞘内注射AM1241 100 pmol/L)。CCI组及不同浓度AM1241处理组大鼠均于鞘内置管7 d之后行坐骨神经结扎,连续14 d鞘内注射,每天2次;分别在术前1 d,术后第1、3、5、7、10、14天注射1 h后测定机械痛阈(MWT),分别在术后第7,14天免疫印迹法(western blot)观察脊髓背角P2X4、P2Y12和P2Y13受体表达变化。结果 1CCI组术后第1、3、5、7、10、14天MWT显著低于假手术组(P<0.05),10 pmol/L AM1241和100 pmol/L AM1241处理组术后第1、3、5、7天MWT明显高于CCI组(P<0.01);但10 pmol/L AM1241处理组术后第10、14天MWT与CCI组相比无明显差异(P>0.05);100 pmol/L AM1241处理组术后第10、14天MWT仍高于CCI组(P<0.05);2与假手术组相比,CCI组术后第7、14天脊髓背角P2X4、P2Y12和P2Y13受体表达显著上调(P<0.01);与CCI组相比,100 mol/L AM1241处理组在术后第7天抑制脊髓背角P2Y12和P2Y13受体表达(P<0.05),在术后第14天抑制背角P2X4受体表达(P<0.05)。结论大麻素CB2受体激动剂AM1241的镇痛效应可能与抑制脊髓背角小胶质细胞P2X4、P2Y12和P2Y13受体表达有关。
Objective To investigate the effect of intrathecal injection AM1241,a selective CB2(Cannabinoid receptor 2) receptor agonist,on mechanical withdrawl threshold(MWT) and the expression of P2X4,P2Y12 and P2Y13receptors in spinal dorsal horn of rats with chronic constriction injury(CCI) of the sciatic nerve.Methods Forty male Sprague-Dawley rats were randomly divided into five groups(n = 8) :sham group(sham operation),CCI group(CCI + intrathecal injection of 0.005% DMSO saline solution),1 pmol / L AM1241 group,(CCI + intrathecal injection of 1 pmol/L AM1241),10 pmol/L AM1241 group(CCI + intrathecal injection of 10 pmol / L AM1241),100 pmol / L AM1241 group(CCI + intrathecal injection of 100 pmol / L AM1241).Rats in CCI group and all AM1241 groups were treated with with chronic constriction injury of the sciatic nerve after 7d of intrathecal tude.The intrathecal injection was administered twice a day for 14 days.MWT were evaluated at1,3,5,7,10 and 14 d after surgery.The expression of P2X4,P2Y12 and P2Y13receptors in dorsal horn was assessed by western blot at 7 and 14 post-operative days.Results 1) MWT in CCI group was significantly lower than sham group at 1,3,5,7,10 and 14 d after surgery(P 0.05).MWT in 10 pmol / L AM1241 group was markedly longer than CCI group at 1,3,5,7 d(P〈 0.01).MWT in 100 pmol / L AM1241 group was significantly longer than CCI group at 1,3,5,7 d and 14 d after surgery(P 〈0.01 at 1,3,5,7 post-operative days;P 〈0.05 at 10,14 post-operative days).2) Compared with the sham group,the P2X4,P2Y12 and P2Y13receptors expression in CCI group were markedly enhanced on 7d and 14 d after surgery(P 〈0.01).Compare with the CCI group,the expression of P2Y12 and P2Y13in 100 pmol / L AM1241 group was suppressed on 7d(P 〈0.01),the expression of P2X4 in 100 pmol / L AM1241 group was suppressed on 14 d after surgery(P〈 0.01).Conclusion Analgesia effect of cannabinoid CB2 receptor agonist AM1241 may be related to the inhibition of the expression of P2X4,P2Y12 and P2Y13receptors in the spinal dorsal horn microglial cells.
出处
《遵义医学院学报》
2015年第3期230-234,238,共6页
Journal of Zunyi Medical University
基金
2012教育部科学技术重点项目(NO:2012125)
2010年贵州省科技厅资助项目(NO:黔科合J字(2010)2264)
遵义医学院重点学科项目(NO:XZXK-20120702)
遵义医学院大学生创新训练重点项目(NO:院发[2014]5807)