奶牛子宫组织a-7nAChR介导LPS上调PGE2合成抑制效应

Inhibitory effect of α-7nAChR on the LPS mediated up-regulation of PGE2 in bovine endometrium

产后奶牛子宫内膜炎是我国奶牛养殖业高发病之一,因此开发防治子宫内膜炎的药物及筛选药物靶点是当前研究热点。前期研究表明,脂多糖(Lipopolysaccharides,LPS)可明显促进奶牛子宫组织前列腺素E2(PGE2)合成,PGE2是炎症反应中疼痛和发热的重要介质,抑制PGE2合成可有效控制炎症损伤。在多种组织中激动α-7烟碱乙酰胆碱受体(α-7 nicotinic acetylcholine receptor,α-7 nAChR)具有抗炎效应,但是否通过PGE2合成途径发挥抗炎作用尚有争议。本研究目的在于调查在LPS刺激奶牛子宫内膜组织中,α-7nAChR能否调控PGE2合成。结果表明,LPS刺激子宫内膜组织12 h IL-6 mRNA表达量最高,因此作本研究炎症模型最佳LPS作用时间;α-7nAChR特异性激动剂PNU-2829875,10和15μmol/L浓度下可显著抑制环氧合酶-2(cyclooxygenase 2,COX-2)和微粒体前列腺素E合成酶-1(Microsomal prostaglandin E synthase-1,m PGES-1)mRNA和蛋白表达及PGE2分泌,该抑制效应可被α-7nAChR特异性抑制剂甲基牛扁碱(MLA)逆转。上述结果表明奶牛子宫内膜组织α-7nAChR可抑制LPS上调PGE2合成效应,是防治奶牛子宫内膜炎潜在的药物靶点。

Endometritis of postpartum dairy cows is one of the high incidence diseases in dairy feeding industry.Therefore,the development of drugs to prevent and treat endometritis as well as the screening of drug targets are the current research hotspots.Previous studies have shown that lipopolysaccharides(LPS)can significantly promote the synthesis of prostaglandin E2(PGE2)in the uterus of dairy cows.PGE2 is an important mediator of pain and fever in inflammatory response.Therefore,inhibition of PGE2 synthesis can effectively control inflammatory injury.Meanwhile,activation ofα-7 nicotinic acetylcholine receptor(α-7 nAChR)in various tissues has anti-inflammatory effect.However,whether it exerts this effect through the synthesis of PGE2 remains controversial.The aim of this study was to investigate thatα-7 nAChR regulates the PGE2 synthesis stimulated by LPS in endometrial tissues of dairy cows.The results showed that the highest expression of IL-6 stimulated by LPS in endometrial tissues was found after 12 h treatment,as the optimal time of LPS administration in an inflammation model in this study.PNU-282987(anα-7 nAChR specific agonist),in concentrations of 5,10 and 15μmol/L,could significantly inhibit the mRNA and protein expression levels of cyclooxygenase-2(COX-2)and microsomal prostaglandin E synthase-1(m PGES-1),as well as PGE2 secretion.These inhibitory effects were reversed by methyltaurine(MLA),a specific inhibitor ofα-7 nAChR.These results suggest thatα-7 nAChR in endometrial tissue of dairy cows could inhibit LPS-induced up-regulation of PGE2 synthesis and is a potential drug target for prevention and treatment of endometritis in dairy cows.