奶牛子宫内膜组织α7-nAChR介导的抗炎效应

Anti-inflammatory effect mediated by α7-nAChR in bovine endometrium

产后奶牛子宫内膜炎高发并导致严重的繁殖机能障碍使该病防治成为当前研究重点。胆碱能抗炎症通路为新药开发提供新的靶点,主要通过烟碱乙酰胆碱受体(α7-nAChR)发挥抗炎作用,但α7-nAChR能否成为治疗奶牛子宫内膜炎的潜在药物靶点尚无数据报道。本研究的目的是调查奶牛子宫内膜组织α7-nAChR是否参与抗炎效应。结果表明,LPS刺激子宫内膜组织8和12 h il-6 mRNA表达量最高,因此选择8和12 h作为本研究炎症模型最佳LPS作用时间;α7-nAChR特异性激动剂PNU-282987在5,10和15mmol/L浓度下可显著下调促炎细胞因子il-1β、il-6、tnf-α及炎症趋化因子il-8 mRNA表达,同时环氧合酶-2(cox-2)和微粒体前列腺素E合成酶-1(mpges-1)表达水平明显下降,这种效应可被α7-nAChR特异性拮抗剂甲基牛扁碱(MLA)逆转。上述结果初步表明激动子宫内膜α7-nAChR具有抑制炎症效应。

Endometritis is a high prevalence and results in severe reproductive dysfunction in postpartum cows.Cholinergic anti-inflammatory pathway provides a novel target to develop pharmacological strategies against inflammatory diseases via α7 nicotinic acetylcholine receptor(α7-nAChR).However,the roles of α7-nAChR in the treatment of endometritis in cows have not been clarified to date.This study aimed to investigate whether α7-nAChR was involved in anti-inflammatory effect in the bovine endometrial tissue.The results showed that LPS elevated the mRNA expression levels of il-6 in the cow endometrium,which reached the peak at 8 and 12 h.Therefore,these time points were taken as the LPS administration periods in this induced inflammation model.Treated with different doses of specific α7-nAChR agonist PNU-282987 5,10 and 15 mmol/L,significantly down-regulated the mRNA levels of proinflammatory cytokines such as il-6,il-1β and tnf-α,as well as chemokine il-8,cyclooxygenase-2(cox-2) and microsomalprostageglandin E synthase-1(mpges-1).Meanwhile,these effects were reversed by the specific α7-nAChR antagonist methyllycaconitine citrate(MLA).Taken together,these results indicated that the stimulation of α7-nAChR exerts a significant anti-inflammatory effect in bovine endometrial tissue.