MRS2211对糖尿病神经病理性疼痛大鼠的镇痛作用及可能的机制  

The analgesic effect of MRS2211 on neuropathic pain in diabetic rats and the related possible mechanisms

作　　者：郭艳娇[1] 王高霞 刘培雯 牛娟[1] 刘晓红[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4期465-469,共5页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(31460266);教育部科学技术重点项目(212154);贵州省科教英才基金(黔省专合字2012-93号);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对糖尿病神经病理性疼痛大鼠机械痛阈及脊髓背角Iba-1和IL-6表达变化的影响。方法:成年SD大鼠随机分为4组(n=8):正常组(仅鞘内注射生理盐水)、药物+正常大鼠组(鞘内注射MRS2211 100 pmol/L)、糖尿病大鼠模型组(diabetes mellitus,DM组)、MRS2211处理组(糖尿病大鼠+鞘内注射MRS2211 100 pmol/L)。SD大鼠单次腹腔注射链脲菌素60 mg/kg,2周后机械痛阈下降认为造模成功。各组大鼠开始鞘内注射生理盐水或MRS2211(100 pmol/L)每周二次,连续4周。在STZ注射前1 d、注射后第2,4,6周末测定给药后机械缩足反射阈值(mechanical withdrawl threshold,MWT);免疫印迹观察STZ注射后2、4、6周末大鼠脊髓背角Iba-1和IL-6表达变化。结果:与正常组相比,DM组MWT明显降低(P<0.01),第2、4、6周末背角Iba-1和IL-6表达也明显上调(P<0.01)。与DM组4周相比,MRS2211处理组MWT明显提高(P<0.01);与DM组6周相比,MRS2211处理组MWT没有明显变化。与DM组4周相比,MRS2211处理组明显抑制STZ注射4周时脊髓背角Iba-1和IL-6表达上调(P<0.01);但与DM组6周相比,MRS2211处理组在STZ注射6周时Iba-1和IL-6表达没有明显变化。结论:鞘内注射P2Y13受体拮抗剂MRS2211可以明显抑制糖尿病大鼠早期的机械痛敏症状,同时脊髓背角Iba-1表达和IL-6表达上调明显减弱。MRS2211有可能通过影响脊髓背角小胶质细胞功能在脊髓水平发挥镇痛作用。Objective： The aim of this study is to investigate the effect of intrathecally injected selective P2Y13 recep- tor antagonist MRS2211 on mechanical withdrawl threshold （MWT） and the expression of Iba-1 and IL-6 in dorsal horn of diabetic rats. Methods ： All rats were randomized into four groups （ n = 8 ） ： normal group （ intrathecal normal saline）, MRS2211 ＋ normal group （intrathecal injection of MRS2211 100 pmol/L, diabetes mellitus group （DM, intrathecal sa- line）, diabetes mellitus ＋ MRS2211 group （intrathecal 100 pmol/L MRS2211 ）. Diabetes mellitus was induced by a single intraperitoneal injection of STZ at a dose of 60 mg/kg. After two weeks, diabetic neuropathic pain model was con- firmed when mechanical pain threshold decreased significantly. Then, MRS2211 （100 pmol/L） or normal saline were in- trathecally administered twice per day for 4 weeks. All rats were tested for mechanical withdrawl threshold （MWT） at the plantar surface of the hindpaw 1 day before and 2th, 4th and 6th week after STZ injection. The expression of Iba-1 and IL-6 in dorsal horn was examined by Western blot on the 2th, 4th and 6th weekend after STZ injection, respectively. Results： MWT in DM group were significantly lower than that in normal group （P 〈 0. 01 ）. Compared with normal group, the expression of Iba-I and IL-6 was significantly increased in dorsal horn on 2th（ P 〈 0.01 ）, 4th（ P 〈 0.01 ） and 6th （P 〈 0.01 ） weekend after STZ injection. Compared with DM group, the MWT were significantly increased after MRS2211 （ 100 pmol/L） administration on 4th weekend （ P 〈 0.01 ）. lntrathecal administration of MRS2211 markedly suppressed the increased expression of Iba-1 and IL-6 at the 4th weekend after STZ injection （ P 〈 0.01 ） as compared with DM. However, intrathecal administration of MRS2211 produced no obvious changes in the increased Iba-1 and IL-6 expression on the 6th weekend after STZ injection. Conclusion： Intrathecal injection of the specific P

关 键 词：糖尿病神经病理性疼痛 P2Y13受体 小胶质细胞 

分 类 号：R587.2[医药卫生—内分泌]