TRPV1/TRPA1对小鼠子宫内膜异位症炎症及疼痛的作用

TRPV1/TRPA1 correlated with inflammation and pain in mice with endometriosis

目的探讨瞬时受体电位锚定蛋白1(transient receptor potential ankyrin 1,TRPA1)和瞬时受体电位香草酸1(transient receptor potential cation channel subfamilyⅤmember 1,TRPV1)异聚体在子宫内膜异位症(简称内异症)小鼠子宫内膜组织中的表达及其与内异症缩宫素介导的疼痛的相关性,同时研究TRPA1和TRPV1对炎症因子的影响。方法建立小鼠内异症模型,予以TRPA1激动剂肉桂醛和TRPA1拮抗剂HC-030031给药干预。疼痛行为学实验检测内异症小鼠扭体次数;ELISA检测血液及腹腔灌洗液炎症因子含量;实时荧光定量PCR及Western blot检测TRPV1/TRPA1基因和蛋白表达;免疫荧光检测TRPV1/TRPA1共定位。结果在内异症模型小鼠中,TRPV1/TRPA1基因和蛋白表达上调,TRPA1激动剂肉桂醛上调TRPV1表达,TRPA1抑制剂HC030031抑制TRPA1的表达。肉桂醛对缓解小鼠内异症疼痛的作用较小,HC030031对疼痛的缓解作用显著。内异症小鼠血清及腹腔灌洗液IL-1β、IL-6、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)和前列腺素(prostaglandin E2,PGE2)的含量显著升高,肉桂醛进一步促进这种作用,而HC030031显著抑制内异症小鼠血清及腹腔灌洗液炎症因子的含量。结论TRPV1、TRPA1为内异症中感知炎症并进行传导的通道;TRPV1/TRPA1异聚体可能有利于响应炎症微环境,进行信号传导,增强疼痛感。

Objective To investigate the correlation between the expression of transient receptor potential ankyrin 1(TRPA1)and transient receptor potential cation channel subfamilyⅤmember 1(TRPV1)isomer in endometrial tissues of mice with endometriosis mediated pain,and to investigate the effect of TRPA1 and TRPV1 on inflammatory factors.Methods Mice endometrium model was established by implantation,TRPA1 agonist cinnamaldehyde and TRPA1 antagonist HC-030031 were administered.Behavior test was carried out to detect the number of writhing;ELISA was used to detect inflammatory factors in blood and peritoneal lavage fluid;TRPV1/TRPA1 gene and protein expression were evaluated by qPCR and Western blot;immunofluorescence detection of TRPV1/TRPA1 co-location were performed.Results The expression of TRPV1/TRPA1 gene and protein in ectopic endometrial tissue was up-regulated.The expression of TRPA1 was up-regulated by cinnamaldehyde,and the expression of TRPA1 was inhibited by HC030031.TRPA1 agonist cinnamaldehyde induced endometriosis in mice less pain relief.The TRPA1 inhibitor HC030031 was more effective in reducing the pain induced by endometriosis.The levels of IL-1β,IL-6,TNF-αand PGE2 in serum and peritoneal lavage fluid of endometriosis mice were significantly increased.Cinnamaldehyde further promoted and HC-030031 significantly inhibited the increasing of inflammatory factors.Conclusion TRPV1 and TRPA1 are signaling paths for sensing and conducting inflammation.TRPV1/TRPA1 may be more conducive to signal transduction in response to the inflammatory microenvironment and enhance pain sensation.