阿托西班对人子宫肌层平滑肌缩宫素受体的调控机制  

The regulatory mechanism of atosiban on oxytocin receptor in human myometrial smooth muscle

作　　者：蒋蕾 吕克蔺 张燕 武菁菁 郭月华 马文革 JIANG Lei;LYU Kelin;ZHANG Yan;WU Jingjing;GUO Yuehua;MA Wenge(Second Department of Division of Production,Shijiazhuang Maternity&Child Healthcare Hospital,Shijiazhuang,Hebei 050000,China)

机构地区：[1]石家庄市妇幼保健院产二科,河北石家庄050000

出　　处：《中国优生与遗传杂志》2021年第12期1690-1696,共7页Chinese Journal of Birth Health & Heredity

基　　金：河北省2019年度医学科学计划课题(20191527)。

摘　　要：目的探讨阿托西班对人子宫肌层平滑肌缩宫素受体的调控机制。方法以子宫肌层细胞为研究对象,进行定量cGAMP细胞中磷酸化ERK(pERK)、PGE_(2)、PGF_(2α)和蛋白激酶A(PKA)、[^(35)S]-GTPγS结合IP-one和IP_(3)的测定。结果在使用缩宫素作为激动剂的竞争性试验中,阿托西班浓度的增加导致缩宫素浓度-反应曲线的峰值、积分和频率向右移动。当缩宫素浓度达到100 nmol/L时,反应达到最大。阿托西班的增加导致曲线向右移动,缩宫素的增加引起了同样的反应。收缩和收缩间隔的初步比较表明,无论收缩程度如何,对照组和阿托西班组的IP_(3)水平基本相同。与空白对照组相比,缩宫素显著提高子宫肌条IP_(3)水平(P<0.05)。PTX预处理逆转了缩宫素、阿托西班和CP93129对cAMP的抑制作用,抑制了缩宫素和阿托西班介导的心肌细胞磷酸化。PTX、U0126和罗非昔单抗抑制COX-2、PGE2和PGF_(2α)的表达。阿托西班使OTR与Gα结合,从而触发人肌层细胞中ERK的激活。结论基于血管加压素V1a和缩宫素的肽拮抗剂阿托西班通过蛋白抑制缩宫素受体的信号传导,可作为Gαi途径信号传导的部分激动剂。Objective To investigate the regulatory mechanism of atosiban on oxytocin receptors in human myometrial smooth muscle.Methods Myometrium cells as the research object,the quantitative determination of phosphorylated ERK(pERK),PGE_(2),PGF_(2α)and protein kinase A(PKA),[^(35)S]-GTPγS combined with IP-one and IP_(3)in cGAMP cells were detected.Results In a competitive trial with oxytocin as an agonist,the increasing concentration of atosiban made the peak,integral,and frequency of the oxytocin concentration-response curve shift to the right.When the oxytocin concentration reached 100 nmol/L,it made maximum reaction.An increasing concentration of atosiban caused the curve shift to the right,and an increasing concentration of oxytocin caused the same response.A preliminary comparison of contraction and contraction interval showed that regardless of the degree of contraction,the IP_(3)levels of the control group and the atosiban group were basically the same.Compared with the blank control group,the IP_(3)level of uterine muscle strips significantly increased because of oxytocin(P<0.05).PTX pretreatment reversed the inhibitory effects of oxytocin,atosiban and CP93129 on cAMP,and inhibited the phosphorylation of cardiomyocytes mediated by oxytocin and atosiban.PTX,U0126 and rofexiimab inhibited the expression of COX-2,PGE_(2)and PGF_(2α).Atosiban made the combination of OTR and Gα,which triggers the activation of ERK in human muscle cells.Conclusion Atosiban,a peptide antagonist based on vasopressin V1 a and oxytocin,inhibits the signal transduction of oxytocin receptors through protein,and can be used as a partial agonist of Gαi pathway signal transduction.

关 键 词：阿托西班 人类子宫平滑肌 受体抑制剂 调控机制 

分 类 号：R711[医药卫生—妇产科学]