鞘内注射MRS2211对慢性坐骨神经结扎大鼠脊髓背角P2X4受体和P38MAPK表达的影响  

Effects of MRS2211 administered intrathecally on the expression of P2X_4 receptor and P38MAPK in dorsal horn of rats with chronic constriction injury of the sciatic nerve

作　　者：王高霞 黄晓莉[1] 刘晓红[1] 田虹[1] 陈远寿[1] 曾俊伟[1] 

机构地区：[1]遵义医学院生理学教研室贵州省麻醉与器官功能保护重点实验室,遵义563000

出　　处：《神经解剖学杂志》2015年第2期225-230,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(31000497,31460266);教育部科学技术重点项目(212154);教育部新世纪优秀人才支持计划(NCET-13-1070);遵义医学院重点学科项目(XZXK-20120702)

摘　　要：目的:观察鞘内注射P2Y13受体阻断剂MRS2211对慢性坐骨神经结扎(CCI)大鼠热痛阈及脊髓背角P2X4受体、P38MAPK表达变化的影响,探讨脊髓P2Y13受体在神经病理性疼痛中的作用。方法:成年SD大鼠随机分为3组(n=8):假手术组、CCI模型组(鞘内注射生理盐水)、MRS2211(100 pmol/L)处理组(CCI+鞘内注射MRS2211)。CCI模型组及MRS2211处理组大鼠均于鞘内置管7 d之后行慢性坐骨神经结扎,连续14 d鞘内注射生理盐水、MRS2211(100 pmol/L),2次/d。分别在术前1 d、术后第1,3,5,7,10,14 d测定给药1h后热缩足潜伏期(TWL);分别在第7,14 d处死大鼠,取脊髓背角做Western Blot检测,观察背角P2X4受体和P38MAPK的表达变化。结果:与假手术组相比,CCI组大鼠第1,3,5,7,10,14 d TWL明显缩短(P<0.01);与CCI组相比,MRS2211处理组大鼠术后第1,3,5,7,10,14 d TWL明显延长(P<0.05)。Western Blot结果观察到,与假手术组相比,CCI组第7 d P2X4受体表达上调(P<0.05),在第14 d P2X4受体表达上调更为明显(P<0.05);与假手术组相比,CCI组第7 d P38MAPK表达明显上调(P<0.05),在第14 d P38MAPK表达有所下降,但与假手术组相比仍具有统计学意义(P<0.05);与CCI组相比,MRS2211处理组大鼠第7 d后背角P38MAPK表达上调明显减弱(P<0.05),但在第14 d P38MAPK表达有所上升,但与CCI组相比仍具有统计学意义(P<0.05);此外,鞘内注射MRS2211并不影响CCI大鼠背角P2X4受体表达变化。结论:鞘内注射P2Y13受体拮抗剂MRS2211可以明显抑制CCI大鼠热痛敏症状和脊髓背角P38MAPK表达的上调,但并不影响CCI大鼠P2X4受体表达变化。这提示MRS2211可以抑制小胶质细胞P38MAPK活化但不影响小胶质细胞P2X4受体表达,这可能是其在脊髓水平发挥镇痛作用的机制之一。Objective： To observe the effects of selective P2Y13 receptor antagonist,MRS2211,injected intrathecally on thermal withdrawal latency（ TWL）,the expression of P2X4 receptor and P38 MAPK in dorsal horn of rats with chronic constriction injury（ CCI） of the sciatic nerve for exploring the role of P2Y13 in neuropathic pain. Methods： SD rats were randomized into three groups（ n = 8） ： sham group（ sham operation,intrathecal normal saline） and CCI group（ CCI ＋intrathecal normal saline）,CCI ＋ MRS2211 group（ intrathecal injection of 100 pmol / L MRS2211）. SD rats in the latertwo groups were intrathecally cathetered at 7 days before sciatic nerve ligation,receiving phsyiological saline or MRS2211（ twice/day） for 14 consecutive days. All rats were tested for hyperalgesia in response to heat on the plantar surface of the hindpaw 1 d before,and 1,3,5,7,10 and 14 days after surgery and TWL were examined at 1h after intrathecal injection. The expression of P2X4 receptor and P38 MAPK in dorsal horn was examined by Western Blot at 7 and 14 days post surgery. Results： TWL in CCI group were significantly lower than those in sham group on post-operative day 1,3,5,7,10 and 14（ P 〈 0. 05）. Repeated intrathecal administration of MRS2211（ 100 pmol / L） markedly suppressed this decrease in TWL at 1,3,5,7 10 and 14 days after nerve injury（ P 〈 0. 01）. The Western Blot results showed the expression of P2X4 receptor and P38 MAPK was markedly enhanced in the ipsilateral dorsal horn on the 7th（ P 〈 0. 01） and 14 th day（ P 〈 0. 01） after nerve injury,being more obviously increased for P2X4 and slightly reduced but still significant change for P38 MAPK on the 14 th day. Repeated intrathecal administration of MRS2211 markedly suppressed the increased expression of P38 MAPK on the 7th（ P 〈 0. 01） and 14 th day（ P 〈 0. 05） after nerve injury,with a slight higher level on the 14 th day. Intrathecal administration of MRS2395 produced no change in the increased P2X4 recept

关 键 词：神经病理性疼痛 P2Y13受体 小胶质细胞 大鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]