祖师麻片对CCI模型大鼠脊髓背角P2X4受体及p38 MAPK表达的影响

Effect of Zushima Tablets on P2X4 Receptor and p38 MAPK Expression in Spinal Dorsal Horn of CCI Rats

目的:研究祖师麻片对慢性挤压神经损伤(CCI)模型大鼠的镇痛作用及机制。方法:采用CCI诱导大鼠坐骨神经损伤,结扎手术完成第8天按痛反应时间(TWT)值随机分为7组(n=12),即对照组、假手术组、模型组、布洛芬组及祖师麻片高、中、低剂量(0.432、0.216、0.108 g·kg-1)组,灌胃给药,每天1次,共给药14次。造模后第20天,测定CCI大鼠患肢(即右后足)的TWT值及50%机械缩足反射阈值(50%MWT)。造模第21天灌注取材,取脊髓段L4~6,利用免疫组化法观察大鼠脊髓背角P2X4和p38丝裂原活化蛋白激酶(p38 MAPK)的表达情况。结果:与模型组比较,祖师麻片各剂量组在给药后各时间点可显著延长模型大鼠患侧的TWT(P<0.01);可提高模型大鼠患侧的50%MWT值(P<0.01);且明显抑制P2X4受体和p38 MAPK在脊髓背角中的表达(P<0.05)。结论:祖师麻片有明显的镇痛作用,能有效降低CCI诱导坐骨神经损伤所致的痛觉敏化,可减轻结扎坐骨神经所致痛觉敏感大鼠患肢对温度刺激、机械刺激的敏感性,其作用机制与其抑制脊髓背角P2X4/p38 MAPK通路有关。

Objective:To observe the pain response time,mechanical withdrawal threshold(50%MWT)and the expression of P2X4 and p38 MAPK in spinal dorsal horn of CCI rats,and elucidate the analgesic effect of Zushima Tablets on CCI model rats and the related mechanism.Methods:Chronic constraining injury of the sciatic nerve model(CCI)was used to induce sciatic nerve injury.On the eighth day after ligation,the sciatic nerve was randomly divided into seven groups according to TWT value(n=12):Control group,sham group,model group,ibuprofen group,Zushima Tablets 0.432,0.216 and 0.108 g·kg-1 group.Rats were given orally once a day for 14 times.On 20th days after model establishment,the pain response time and 50%MWT of affected limbs(right hind foot)of CCI rats were measured.At the 21st day of modeling,perfusion materials were collected from the spinal cord segment L4-6,the expression of P2X4 and p38 MAPK in spinal dorsal horn of rats was observed by immunohistochemical method.Results:Zushima Tablets can significantly prolong the pain response time of the affected side of model animals at different time points after administration(P<0.01),and the 50%MWT value of the affected side of the model animal was increased after administration(P<0.01).The expression of P2X4 receptor and p38 MAPK in the spinal dorsal horn of the model animal was significantly inhibited(P<0.05).Conclusion:Zushima Tablets has obvious analgesic effect and can effectively reduce pain sensitization caused by sciatic nerve injury.It can alleviate the sensitivities of affected limbs to temperature and mechanical stimulation induced by sciatic nerve ligation in rats.Its mechanism is related to the inhibition of P2X4/p38 MAPK pathway in spinal dorsal horn.