皖南地区眼镜蛇毒活性组分外用镇痛的效应及机制研究
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摘要
目的:探讨皖南地区眼镜蛇毒活性组分(cobra venom analgesic factor,CVAF)外用镇痛的效应及其可能的作用机制。方法:雄性SD大鼠分为生理盐水对照组(NS组)、完全弗氏佐剂炎痛组(CFA组)、双氯芬酸钠镇痛阳性对照组(CFA+SL组)、氟比洛芬镇痛阳性对照组(CFA+FB组)、CVAF镇痛实验组(CFA+CVAF组),比较观察CVAF凝胶局部外用的镇痛效果。分别采用热刺痛仪及机械压痛仪测定各组大鼠痛阈,ELISA法检测各组大鼠脊髓匀浆中IL-1、TNF-α的含量,HE染色法观察大鼠足趾组织病理变化。结果:与CFA组比较,CVAF镇痛组大鼠在给药后的第7日和第14日的体质量差异具有统计学意义(P <0. 05、P <0. 01),CVAF组大鼠的机械压痛阈和热痛阈都有所提高(P <0. 01),脊髓匀浆中IL-1、TNF-α的浓度相对减少,差异有统计学意义(P <0. 01),在HE染色中,CVAF组大鼠足趾组织水肿明显减轻,炎性浸润相对不显著。结论:皖南地区CVAF凝胶局部外用可提高炎痛大鼠热痛阈和机械压痛阈,其机制可能与减少炎症介质释放,抑制炎症反应有关。
AIM: To explore the effect of topical analgesia of cobra venom analgesic factor( CVAF) in southern Anhui province and its possible mechanism. METHODS: Male SD rats were divided into normal saline control group( NS group), complete Freund ' s adjuvant pain group( CFA group),diclofenac sodium analgesic positive control group( CFA + SL group),flurbiprofen analgesic positive control group( CFA + FB group),CVAF analgesia group( CFA + CVAF group). The analgesic effect of CVAF gel,the active component of cobra venom was observed and compared. The pain thresholds of rats in each group were measured with a thermal tingling tester and mechanical tenderness tester. The content of IL-1 and TNF-α in the homogenate of spinal cord in each group was detected by using ELISA,the pathological changes of rat toe tissue was observed by using HE staining. RESULTS: Compared with CFA group,the weight loss of CVAF analgesia rats on the 7 th and 14 th day after administration was improved( P < 0. 05, P <0. 01). The mechanical pain threshold and the thermal pain threshold of the CVAF group were all improved( P < 0. 01). The concentrations of IL-1 and TNF-α in the homogenate of spinal cord were relatively low( P < 0. 01). In HE staining,the toe tissue edema in the CVAF group was significantly reduced,and the inflammatory infiltration was relatively insignificant. CONCLUSION: The CVAF gel,the active ingredient of Cobra venom in southern Anhui province,can improve the inflammatory pain in rats hot pain threshold and mechanical pressure threshold; its mechanism may be related to reduce the release of inflammatory mediators,inhibiting the inflammatory response.
AIM: To explore the effect of topical analgesia of cobra venom analgesic factor( CVAF) in southern Anhui province and its possible mechanism. METHODS: Male SD rats were divided into normal saline control group( NS group), complete Freund ' s adjuvant pain group( CFA group),diclofenac sodium analgesic positive control group( CFA + SL group),flurbiprofen analgesic positive control group( CFA + FB group),CVAF analgesia group( CFA + CVAF group). The analgesic effect of CVAF gel,the active component of cobra venom was observed and compared. The pain thresholds of rats in each group were measured with a thermal tingling tester and mechanical tenderness tester. The content of IL-1 and TNF-α in the homogenate of spinal cord in each group was detected by using ELISA,the pathological changes of rat toe tissue was observed by using HE staining. RESULTS: Compared with CFA group,the weight loss of CVAF analgesia rats on the 7 th and 14 th day after administration was improved( P < 0. 05, P <0. 01). The mechanical pain threshold and the thermal pain threshold of the CVAF group were all improved( P < 0. 01). The concentrations of IL-1 and TNF-α in the homogenate of spinal cord were relatively low( P < 0. 01). In HE staining,the toe tissue edema in the CVAF group was significantly reduced,and the inflammatory infiltration was relatively insignificant. CONCLUSION: The CVAF gel,the active ingredient of Cobra venom in southern Anhui province,can improve the inflammatory pain in rats hot pain threshold and mechanical pressure threshold; its mechanism may be related to reduce the release of inflammatory mediators,inhibiting the inflammatory response.
引文
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[16]王海华,张根葆,闵志雪,等.皖南地区眼镜蛇毒镇痛组分对大鼠炎性痛作用机制探讨[J].中国临床药理学与治疗学,2013,18(10):1093-1099.
[2]蒋世强,潘能庆,鄢航,等.眼镜蛇神经毒素研究进展[J].现代农业科技,2017,17(4):255-256.
[3]丁晓兰,孙美玲,秦正红.中华眼镜蛇毒口服给药镇痛作用的研究[J].抗感染药学,2013,10(3):180-183.
[4]饶荣,杨祥良,刘卫.多肽蛋白质药物口服纳米载药系统研究进展[J].医药导报,2018,37(6):697-702.
[5]赵子佳,边学峰,李晶峰,等.蛋白肽类药物及其给药途径研究进展[J].吉林中医药,2018,38(2):188-190.
[6]闵志雪,黄璐,孙瑶,等.皖南地区眼镜蛇毒活性组分镇痛效应的初步研究[J].中国病理生理杂志,2013,29(1):150-154.
[7] Bráz JM,Sharif-Naeini R,Vogt D,et al. Forebrain GABAergic neuron precursors integrate into adult spinal cord and reduce injury-induced neuropathic pain[J]. Neuron,2012,74(4):663-675.
[8] Woolf CJ,Salter MW. Neuronal plasticity:increasing the gain in pain[J]. Science,2000,288(5472):1765-1769.
[9] Cirino G,Distrutti E,Wallace JL. Nitric oxide and inflammation[J]. Inflamm Allergy Drug Targets,2006,5(2):115-119.
[10] Miller RE,Miller RJ,Malfait AM. Osteoarthritis joint pain:The cytokine connection[J]. Cytokine,2014(70):185-193.
[11] Stephens K,Cooper BA,West C,et al. Associations between cytokine gene variations and severe persisten breast pain in women following breast cancer surgery[J]. J Pain,2014,15(2):169-180.
[12] Finco D,Grimaldi C,Fort M,et al. Cytokine release assays:Current practices and future directions[J]. Cytokine,2014,66(2):143-155.
[13] Lee AS,Ellman MB,Yan DY,et al. A current review of molecular mechanisms regarding osteoarthritis and pain[J]. Gene,2013,527(2):440-447.
[14] Subang MC,Richardson PM. Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue[J]. Eur J Neurosci,2001,13(3):521-528.
[15] Youn DH,Wang H,Jeong SJ. Exogenous tumor necrosis factor-alpha rapidly alters synaptic and sensory transmission in the adult rat spinal cord dorsal horn[J]. J Neurosci Res,2008,86(13):2867-2875.
[16]王海华,张根葆,闵志雪,等.皖南地区眼镜蛇毒镇痛组分对大鼠炎性痛作用机制探讨[J].中国临床药理学与治疗学,2013,18(10):1093-1099.