[1]李思海,杨　军,魏　娅.地佐辛对神经病理性疼痛大鼠的镇痛作用及对Toll样受体4/核转录因子-κB信号通路的影响[J].新乡医学院学报,2019,36(4):309-314.[doi:10.7683/xxyxyxb.2019.04.003]
　LI Si-hai,YANG Jun,WEI Ya.Effect of dezocine on neuropathic pain and Toll-like receptor 4/nuclear factor-κB signaling pathway in rats[J].Journal of Xinxiang Medical University,2019,36(4):309-314.[doi:10.7683/xxyxyxb.2019.04.003]
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地佐辛对神经病理性疼痛大鼠的镇痛作用及对Toll样受体4/核转录因子-κB信号通路的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年4
页码:
309-314
栏目:
基础研究
出版日期:
2019-04-05

文章信息/Info

Title:
Effect of dezocine on neuropathic pain and Toll-like receptor 4/nuclear factor-κB signaling pathway in rats
作者:
李思海; 杨　军; 魏　娅
（河南中医药大学第三附属医院麻醉科，河南　郑州　450000）
Author(s):
LI Si-hai; YANG Jun; WEI Ya
（Department of Anesthesiology，the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine，Zhengzhou 450000，Henan Province，China）
关键词:
地佐辛; 神经病理性疼痛; 大鼠; Toll样受体4; 核转录因子-κB
Keywords:
dezocine; neuropathic pain; rats; Toll-like receptor 4; nuclear factor-κB
分类号:
R965
DOI:
10.7683/xxyxyxb.2019.04.003
文献标志码:
A
摘要:
目的　探讨地佐辛对神经病理性疼痛大鼠的镇痛作用及对Toll样受体4（TLR4）/核转录因子-κB（NF-κB）信号通路的影响。方法　将90只Sprauge Dawley大鼠随机分为假手术组、模型组、普瑞巴林组及地佐辛低、中、高剂量组，每组15只。模型组、普瑞巴林组及地佐辛低、中、高剂量组大鼠结扎左侧第5腰神经制备神经病理性疼痛模型，假手术组大鼠不结扎第5腰神经。术后第4天开始，普瑞巴林组大鼠腹腔注射普瑞巴林18 mg·kg-1·d-1，地佐辛低、中、高剂量组大鼠分别注射地佐辛6、12、24 mg·kg-1·d-1，模型组及假手术组大鼠注射等剂量氯化钠溶液；注射量均为1 mL·kg-1，连续给药7 d。分别于术前及术后第4、11天测定各组大鼠机械痛阈值（MWT）和热缩足反射潜伏期（TWL）；术后第11天处死各组大鼠并取脊髓组织，采用酶联免疫吸附试验法检测脊髓组织中白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）及肿瘤坏死因子-α（TNF-α）水平，Western blot法检测脊髓组织中TLR4、NF-κB蛋白相对表达量。结果　各组大鼠术前MWT、TWL比较差异无统计学意义（F=0.261、0.662，P>0.05）。术后第4、11天，模型组、普巴瑞林组及地佐辛低、中、高剂量组大鼠MWT、TWL显著低于术前（P<0.05），模型组、普瑞巴林组及地佐辛低、中、高剂量组大鼠的MWT、TWL显著低于假手术组（P<0.05）。术后第4天，模型组、普瑞巴林组及地佐辛低、中、高剂量组大鼠MWT、TWL比较差异均无统计学意义（P>0.05）。术后第11天，模型组大鼠MWT显著低于术后第4天，普巴瑞林组及地佐辛中、高剂量组大鼠MWT、TWL显著高于术后第4天（P<0.05）。术后第11天，普瑞巴林组及地佐辛低、中、高剂量组大鼠MWT、TWL显著高于模型组（P<0.05），普瑞巴林组及地佐辛中、高剂量组大鼠MWT、TWL显著高于地佐辛低剂量组（P<0.05），普瑞巴林组及地佐辛高剂量组大鼠MWT、TWL显著高于地佐辛中剂量组（P<0.05），地佐辛高剂量组大鼠MWT、TWL与普瑞巴林组比较差异无统计学意义（P>0.05）。模型组、普瑞巴林组及地佐辛低、中、高剂量组大鼠脊髓组织中IL-6、MCP-1、TNF-α水平和TLR4蛋白、NF-κB蛋白相对表达量均显著高于假手术组（P<0.05），普瑞巴林组及地佐辛低、中、高剂量组大鼠脊髓组织中IL-6、MCP-1、TNF-α水平和TLR4蛋白、NF-κB蛋白相对表达量显著低于模型组（P<0.05），普瑞巴林组及地佐辛中、高剂量组大鼠脊髓组织中IL-6、MCP-1、TNF-α水平和TLR4蛋白、NF-κB蛋白相对表达量显著低于地佐辛低剂量组（P<0.05），普瑞巴林组及地佐辛高剂量组大鼠脊髓组织中IL-6、MCP-1、TNF-α水平和TLR4蛋白、NF-κB蛋白相对表达量显著低于地佐辛中剂量组（P<0.05），地佐辛高剂量组与普瑞巴林组大鼠脊髓组织中IL-6、MCP-1、TNF-α水平及TLR4蛋白、NF-κB蛋白相对表达量比较差异无统计学意义（P>0.05）。结论　地佐辛可能通过抑制TLR4/NF-κB信号通路的激活而减轻脊髓炎症反应，提高神经病理性疼痛大鼠MWT，延长TWL，发挥镇痛作用。
Abstract:
Objective　To investigate the analgesic effect of dizosin on neuropathic pain （NPP） rats and its effect on Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） pathway.Methods　Ninety Sprauge Dawley rats were randomly divided into sham operation group，model group，pregabalin group，low dose dezocine group，medium dose dezocine group and high dose dezocine group，with 15 rats in each group.The NPP models were established by ligating the left fifth lumbar nerve of rats in model group，pregabalin group and low，medium and high dose dezocine groups.The rats in the sham operation group weren′t performed with the fifth spinal nerve ligation.On the fourth day after operation，the rats in the pregabalin group were intraperitoneally injected with pregabalin（18 mg·kg-1·d-1），and the rats in the low，medium and high dose dezocine groups were injected with dizosin（6，12 and 24 mg·kg-1·d-1），respectively.The rats in the model group and sham operation group were injected with the same dose of sodium chloride solution.The injection volume was 1 mL·kg-1 in each group，continuous injection for 7 days.The mechanical withdrawal threshold （MWT） and the thermal withdrawal latency （TWL） were measured at the time points of before operation and the fourth，eleventh day after operation.On the eleventh day after operation，rats in each group were sacrificed and the spinal cord tissues were taken.The levels of interleukin-6 （IL-6），monocyte chemoattractant protein-1 （MCP-1） and tumor necrosis factor-α （TNF-α） in spinal cord tissues were detected by enzyme-linked immunosorbent assay.The relative expression of TLR4 and NF-α protein in spinal cord tissues were detected by Western blot.Results　There was no significant difference in MWT and TWL of rats among the groups before operation （F=0.261，0.662；P> 0.05）.On the fourth and eleventh day after operation，the MWT and TWL of rats in the model group，preparerin group and the low，medium，high dose dzocine group were significantly lower than those before operation （P<0.05）；the MWT and TWL of rats in the model group，preparerin group and the low，medium and high dose dzocine group were significantly lower than those in the sham operation group （P<0.05）.On the fourth day after operation，there was no significant difference in MWT and TWL among the model group，pregabalin group and the low，medium and high dose dezocine groups （P>0.05）.The MWT on the eleventh day after operation was significantly lower than that on the fourth day after operation in the model group.The MWT and TWL on the eleventh day after operation were significantly higher than those on the fourth day after operation in the preparing group and the medium and high dose dezocine group （P<0.05）.On the eleventh day after operation，the MWT and TWL of rats in the pregabalin group and the low，medium and high dose dezocine groups were significantly higher than those in the model group （P<0.05）；the MWT and TWL of rats in the pregabalin group，the medium and high dose dezocine groups were significantly higher than those in the low dose dezocine group （P<0.05）；the MWT and TWL of rats in the pregabalin group and high dose dezocine group were significantly higher than those in the medium dose dezocine group（P<0.05）；there was no significant difference in MWT，TWL between the pregabalin group and high dose dezocine group （P>0.05）.The levels of IL-6，MCP-1，TNF-α and the relative expression of TLR4 and NF-κB in spinal cord tissues of rats in the model group，pregabalin group and the low，medium and high dose dezocine groups were significantly higher than those in the sham operation group （P<0.05）.The levels of IL-6，MCP-1，TNF-α and the relative expression of TLR4 and NF-κB in spinal cord tissues of rats in the pregabalin group and the low，medium and high dose dezocine groups were significantly lower than those in the model group （P<0.05）.The levels of IL-6，MCP-1，TNF-α and the relative expression of TLR4 and NF-κB in spinal cord tissues of rats in the pregabalin group and the medium and high dose dezocine groups were significantly lower than those in the low dose dezocine group （P<0.05）.The levels of IL-6，MCP-1，TNF-α and the relative expression of TLR4 and NF-κB in spinal cord tissues of rats in the pregabalin group and the high dose dezocine group were significantly lower than those in the medium dose dezocine group （P<0.05）.There was no significant difference in the levels of IL-6，MCP-1，TNF-α and the relative expression of TLR4 and NF-κB in spinal cord tissues of rats between the high dose dezocine group and the pregabalin group （P<0.05）.Conclusion　Dizocine may play an analgesic role by inhibiting the activation of TLR4/NF-κB signaling pathway，alleviating spinal inflammation，increasing the MWT，and prolonging the TWL in rats with neuropathic pain.

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更新日期/Last Update: 2019-04-05