基于CN/IL-10信号途径探讨乌司他丁对神经性疼痛大鼠模型的镇痛效应及作用机制  

Analgesic Effect and Mechanism of Ulinastatin on Neuropathic Pain Rat Model Based on CN/IL-10 Signaling Pathway

作　　者：黄钰媛 韦雪梅 郑育秀 刘丽丽[1] HUANG Yuyuan;WEI Xuemei;ZHENG Yuxiu(The Second Affiliated Hospital of Hainan Medical College, Hainan Haikou 570311, China)

机构地区：[1]海南医学院第二附属医院麻醉科,海南海口570311

出　　处：《河北医学》2022年第2期177-182,共6页Hebei Medicine

基　　金：海南省基础与应用基础研究计划项目,(编号:818QN319);国家自然科学基金委员会资助项目,(编号:81660820)。

摘　　要：目的:探讨乌司他丁(UTI)对神经性疼痛大鼠的镇痛效应及其相关分子机制。方法:将40只SD大鼠随机分为假手术组(Sham组)、模型组(CCI组)、UTI组、UTI+他克莫司(FK506)组,每组10只。除Sham组外,其它各组大鼠构建慢性坐骨神经结扎(CCI)模型,各组大鼠给予相应给药处理后,采用疼痛行为测量法测定大鼠疼痛行为变化,苏木精-伊红(HE)染色法检测大鼠坐骨神经组织形态学变化,酶联免疫吸附法(ELISA)检测大鼠坐骨神经组织中白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)水平,原位缺口末端标记法(TUNEL)检测大鼠坐骨神经组织细胞凋亡情况,免疫印迹法(Western blot)检测大鼠坐骨神经组织钙调神经磷酸酶(CN)和白介素-10(IL-10)蛋白表达水平。结果:UTI能够降低CCI诱导的大鼠神经性疼痛,减轻坐骨神经组织病理性损伤,降低坐骨神经组织中IL-6、IL-1β、TNF-α水平,减少坐骨神经细胞凋亡数,并能够显著上调神经性疼痛大鼠坐骨神经组织中CN和IL-10蛋白表达量,差异均有统计学意义(P<0.05)。CN抑制剂FK506可减弱UTI对神经性疼痛大鼠的作用效果,下调神经性疼痛大鼠坐骨神经组织中CN和IL-10蛋白表达量,差异均有统计学意义(P<0.05)。结论:UTI可能通过调控CN/IL-10信号途径减轻神经性疼痛大鼠的炎症反应和细胞凋亡,进而缓解大鼠神经性疼痛。Objective:To investigate the analgesic effect of ulinastatin(UTI)on rat model of neuropathic pain and its related molecular mechanism.Methods:Forty SD rats were randomly divided into sham group,CCI group,UTI group and UTI+Tacrolimus(FK506)group,with 10 rats in each group.Except sham group,chronic constriction injury(CCI)model was established in other groups,after the rats in each group were given the corresponding treatment,the changes of pain behavior were measured by pain behavior measurement,the morphological changes of sciatic nerve tissue were detected by hematoxylin eosin(HE)staining,and the levels of interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in sciatic nerve tissue were detected by enzyme-linked immunosorbent assay(ELISA);TdT-mediated dUTP nick end labeling(TUNEL)was used to detect the apoptosis of rat sciatic nerve;Western blot was used to detect the protein expression of calcineurin(CN)and interleukin-10(IL-10).Results:UTI can reduce CCI induced neuropathic pain in rats,alleviate the pathological injury of sciatic nerve tissue,and reduce the levels of IL-6,IL-1βand TNF-αin sciatic nerve tissue,and decrease the number of apoptosis of sciatic nerve cells,the expression of CN and IL-10 protein in sciatic nerve tissue of rats with neuropathic pain was significantly up-regulated,the difference was statistically significant(P<0.05).FK506,an inhibitor of CN,attenuated the effect of UTI on neuropathic pain rats,and down-regulated the protein expression of CN and IL-10 in sciatic nerve tissue of neuropathic pain rats,the difference was statistically significant(P<0.05).Conclusion:UTI may reduce inflammation and apoptosis in neuropathic pain rats by regulating CN/IL-10 signaling pathway,and then alleviate the neuropathic pain of rats.

关 键 词：乌司他丁 神经性疼痛 镇痛效应 坐骨神经 CN/IL-10信号途径 

分 类 号：R28[医药卫生—中药学]