右美托咪定通过P2X7R-Slit1通路改善糖尿病大鼠神经病理性疼痛的研究  

Study of Dextropyrimidine Improving Neuropathic Pain in Diabetes Rats through P2X 7 R-Slit1 Pathway

作　　者：魏海翔[1] 詹丽花 张旭韬 程章仁 李丹 何义 姜闽英[1] WEI Hai-xiang;ZHAN Li-hua;ZHANG Xu-tao;CHEN Zhang-ren;LI Dan;HE Yi;JIANG Min-ying(Department of Anesthesiology,First Hospital of Nanping City,Nanping 353000,China;School of Basic Medicine,Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]福建省南平市第一医院麻醉科,福建医科大学附属南平市第一医院,福建南平353000 [2]福建医科大学基础医学院,福建福州350122

出　　处：《海峡药学》2023年第8期27-30,共4页Strait Pharmaceutical Journal

基　　金：福建省医学创新课题资助项目(编号:2020CXB041);福建省自然科学基金项目(编号:2023J011874)。

摘　　要：目的 探讨右美托咪定(DEX)对糖尿病神经病理性疼痛(DNP)大鼠的改善作用及对嘌呤能离子通道型受体7(P2X7R)/Slit分泌蛋白家族1(Slit1)信号通路的影响。方法 腹腔注射链脲佐菌素溶液制备DNP大鼠模型成功后,随机分为模型对照(Model)组、DEX 50μg·kg-1组和P2X7R阻断剂40 mg·kg-1组,每组6只,另取6只SD大鼠设为正常对照(Control)组,每天予相应药物或生理盐水1次,连续21 d。通过机械性疼痛刺激试验检测各组大鼠缩爪阈值;以苏木精-伊红(HE)染色法检测坐骨神经病理形态学情况;酶联免疫吸附法(ELISA)测定血清中炎性因子白细胞介素-6(IL-6)和IL-1β含量;蛋白免疫印迹法检测脊髓背角组织中P2X7R和Slit1蛋白表达。结果 与Control组相比,Model组大鼠缩爪阈值明显降低,坐骨神经细胞排列紊乱、血清中IL-6和IL-1β含量、脊髓背角组织P2X7R、Slit1明显升高(均P<0.001);与Model组比较,DEX组和P2X7R阻断剂组大鼠缩爪阈值显著提高(P<0.001)、坐骨神经结构较完整,IL-6和IL-1β含量(P<0.001)与脊髓背角组织P2X7R、Slit1蛋白表达明显降低(P<0.05)。结论 DEX可抑制DNP大鼠炎症反应,减少脊髓背角神经细胞凋亡,减轻疼痛症状,可能是通过下调P2X7R/Slit1通路实现的。OBJECTIVE To investigate the effect of dexmedetomidine on neuropathic pain(DNP)and purinergic ion channel receptor 7(P2X 7R)/Slit secretory protein family 1(Slit1)signaling pathway in diabetes rats.METHODS After the preparation of DNP rat model by intraperitoneal injection of streptozotocin solution,the rats were randomly divided into model control group and dexmedetomidine 50μg·kg-1 group,P2X 7R blocker 40 mg·kg-1 group,6 rats in each group,another 6 rats as normal control group,given corresponding drugs or physiological saline once a day for 21 days.The mechanical withdrawal threshold of rats was measured by mechanical pain stimulation test;The pathological changes of the sciatic nerve in each group were detected by hematoxylin-eosin(HE)staining;The content of inflammatory factors interleukin-6(IL-6)and IL-1βin rat serum was determined by enzyme linked immunosorbent assay(ELISA);The key protein expression of P2X 7R-Slit1 pathway in rat spinal dorsal horn was detected by Western blot.RESULTS Compared with the normal control group,the mechanical withdrawal threshold of rats in the model group was significantly lower,the arrangement of sciatic nerve cells was disordered,the contents of IL-6 and IL-1βin serum,P2X 7R and Slit1 in the spinal dorsal horn tissue were significantly higher in the model group(all P<0.001);Compared with the model group,the mechanical withdrawal threshold of rats in DEX group and P2X 7R inhibitor group was significantly increased(P<0.001),the sciatic nerve structure was more complete,the content of IL-6 and IL-1β(P<0.001)and the expression of P2X 7R and Slit1 protein in spinal dorsal horn tissue were significantly decreased(P<0.05).CONCLUSION Dexmedetomidine can inhibit inflammatory reaction,reduce neuronal apoptosis in spinal dorsal horn and alleviate pain symptoms in diabetes rats,which may be achieved by down-regulation of P2X 7R/Slit1 pathway.

关 键 词：1型糖尿病 神经病理性疼痛 通路 右美托咪定 大鼠 

分 类 号：R965[医药卫生—药理学]