氯胺酮对糖尿病神经痛大鼠p38丝裂原活化蛋白激酶表达的影响

Effects of Ketamine on Expression of p38 Mitogen-Activated Protein Kinase in Diabetic Peripheral Neuropathy Rats

目的:观察氯胺酮对糖尿病神经病理痛大鼠神经系统中p38丝裂原活化蛋白激酶(p38MAPK)的影响,探讨其作用的信号机制。方法:16只雌性Wistar大鼠注射链脲菌素复制糖尿病神经病理痛模型。随机分为糖尿病组(D组)和氯胺酮组(K组),另设对照组(C组)。K组大鼠经氯胺酮处理。均测机械痛阈和神经传导速度(NCV),免疫组化和ELISA法检测脊髓和背根神经节(DRG)磷酸化p38MAPK(p-p38MAPK)水平。结果:与对照组比较,糖尿病组和氯胺酮组MWT和NCV均下降,脊髓和DRG中p-p38MAPK水平均升高(P<0.05),但糖尿病组变化幅度明显(P<0.05)。结论:氯胺酮对大鼠糖尿病神经病理痛有疼痛治疗和神经保护作用,其机制可能是阻断p38MAPK信号通路。

Objective To observe the effect of ketamine on expression of p38Mitogen-Activated Protein Kinase （p38MAPK） in diabetic peripheral neuropathy rats. Methods The diabetic peripheral neuropathy model was established by injecting streptozotocin in 16 female Wistar rats ,then randomly divided into three groups：diabetic neuropathic pain group（ D group）, ketamine group （K group ） treated with ketamine, and control group （C group ）. Paw withdrawal mechanical threshold （MWT） and nerve conduction velocity（NCV） were measured. The level of phosphorylated p38MAPK in spinal cord and dorsal root ganglion was assessed by immunohistochemestry and ELISA. Results Compared with control group, MWT and NCV of rats were all significantly decreased,whereas the level of p-p38MAPK in spinal cord and dorsal root ganglion were all significantly increased in group D and group K,but the extent of the change of p-p38MAPK in gruop D was more obvious. Conclusion Ketamine can effectively relieve pain and plays a protective role in peripheral neuropathy of diabetes, the mechanism is probably through blocking the p38MAPK signal pathway.