电针对糖尿病神经痛模型大鼠背根神经节磷酸化p38丝裂原活化蛋白激酶的干预作用

Effect of Electroacupuncture on the Phosphorylation of p38 Mitogen-Activated Protein Kinase in the Dorsal Root Ganglion of Rats with Diabetic Neuropathic pain

目的观察电针对糖尿病神经痛大鼠背根神经节磷酸化p38丝裂原活化蛋白激酶(pp38MAPK)表达的影响。方法将20只健康雄性SD大鼠按随机数字表法分为空白组6只,造模组14只,造模组大鼠采用单次腹腔注射链脲佐菌素(65mg/kg)建立糖尿病神经痛模型,造模成功的12只大鼠按随机数字表法分为模型组和电针组,每组6只;电针组于2周后介入电针,取双侧足三里和昆仑穴,每天1次,每次30min,干预1周。空白组、模型组大鼠予以同电针组相同的固定。采用动态足底触觉仪检测大鼠造模前、造模后1、2、3周机械痛阈,采用免疫荧光法检测大鼠腰4至腰6背根神经节中p-p38MAPK阳性细胞表达。结果与空白组比较,造模后1周模型组和电针组大鼠机械痛阈[(31.06±0.66)g、(32.51±0.84)g比(31.04±1.63)g,P>0.05]无显著性差异,造模后2、3周模型组大鼠机械痛阈[(25.20±1.03)g比(31.17±0.68)g,(18.29±2.01)g比(31.92±0.95)g,P均<0.05]均显著降低;与模型组比较,造模后3周电针组大鼠机械痛阈[(26.91±2.81)g比(18.29±2.01)g,P<0.05]显著升高。与空白组比较,模型组大鼠L4-L6背根神经节上的p-p38MAPK阳性细胞个数[(37.76±0.38)个比(21.49±1.57)个、(35.63±1.84)个比(22.49±2.66)个、(33.95±1.34)个比(21.79±1.09)个,P均<0.05]表达显著升高;与模型组比较,电针组大鼠腰4至腰6背根神经节上的p-p38MAPK阳性细胞个数[(26.69±1.35)个比(37.76±0.38)个、(23.54±3.22)个比(35.63±1.84)个、(26.38±2.65)个比(33.95±1.34)个,P均<0.05]表达显著降低。结论电针对糖尿病神经痛模型大鼠有良好的镇痛效果,其机制可能与抑制背根神经节神经元p-p38MAPK表达相关。

Objective To assess the effects of the electroacupuncture(EA)on changes in the expression of phospholyrated-p38 mitogen activation protein kinase(p-p38MAPK)in the dorsal root ganglia(DRG)of a rat model of diabetic neuropathic pain(DNP).Methods Twenty male Sprague-Dawley rats were randomly divided into the Control(n=6)and the model groups(n=14).The model rats were induced by a single streptozotocin intraperitoneal injection(65mg/kg)to establish DNP model,resulting in 12 alive DNP rats,which were further divided into the DNP control and EA groups using the random number table(n=6 in each group).The EA rats were subjected to the EA treatment two weeks later at the acupoints of Zusanli and Kunlun for 30 min daily for a week according to the Practical acupuncture handbook.The rats were monitored and subjected to the measurement of the fasting blood glucose level and the paw withdrawal thresholds(PWT)test before and 1,2,and 3 weeks after streptozotocin in jections.The immunofluorescence was performed to detect p-p38MAPK expression in rat L4-L6 DRG at 3 weeks after modeling.Results The fasting blood glucose was significantly increased in the model rats after modeling(P>0.05).There was no significant difference in the PWT of all three groups of rats(31.06±0.66,32.51±0.84,and 31.04±1.63,respectively;P>0.05)before modeling,but the PWT number was significantly reduced in the DNP rats(25.20±1.03 vs.31.17±0.68g and 18.29±2.01 vs.31.92±0.95g;P<0.05)at Week 2 and 3 and the PWT in the EA rats was significantly increased after a week treatment compared to the DNP group(26.91±2.81 vs.18.29±2.01g;P<0.05).Furthermore,compared with the control,level of p-p38MAPK expression was significantly increased in the rat L4-L6 DRG of the DNP group(37.76±0.38 vs.21.49±1.57,35.63±1.84 vs.22.49±2.66,and 33.95±1.34 vs.21.79±1.09,respectively;P<0.05),but the EA treatment significantly reduced expression of p-p38MAPK in L4-L6 DRG compared to DNP control(26.69±1.35 vs.37.76±0.38,23.54±3.22 vs.35.63±1.84,26.38±2.65 vs.33.95±1.34,respectively;P<0.05).Conclusion The EA treatment possessed significant analgesia for DNP and the underlying molecular event might be due to inhibition of the upregulated expression of p-p38MAPK in DRG.