Prostaglandin D2 evokes potent uterine contraction via the F prostanoid receptor in postpartum rats
Prostaglandin D2 evokes potent uterine contraction via the F prostanoid receptor in postpartum rats
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前列腺素 D-2 通过 F 类前列腺素受体在产后大鼠中引起强烈的子宫收缩
DOI：
10.1016/j.ejphar.2018.08.012
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Hu C;Liu B;Li H;Wu X;Guo T;Luo W;Zhou Y
前列腺素（PG）D2是一种已知具有消肿作用的前列腺素类，可通过上调F前列腺素类（FP）受体引起体外子宫平滑肌收缩增加。本研究进一步测定了产后大鼠子宫对PGD2的反应，以评估前列腺素类成为产后子宫收缩乏力治疗剂的可能性，产后子宫收缩乏力是产后出血的主要原因，可导致母体发病。在体外和体内测定产后子宫对PGD2的反应，并与产后大鼠的子宫反应进行比较。在这里，我们表明，在产后子宫肌条PGD2引起的收缩敏感FP受体拮抗剂。有趣的是，这种反应不仅在很大程度上超过了子宫收缩大鼠，而且与PGF 2 α获得的收缩相当，PGF 2 α是一种产后子宫收缩乏力的治疗药物，但在包括高血压在内的疾病中与之矛盾。事实上，PGD2也被发现在体内条件下引起基础子宫收缩的增加。Western blot结果显示，产后大鼠子宫肌层FP受体的表达高于产后大鼠。此外，我们注意到，产后子宫中产生的PGD2的量，虽然低于产后大鼠，但与非妊娠条件相比有所增加。因此，这些结果表明，由于子宫肌层FP受体的进一步上调或高表达，PGD2可以引起产后子宫有力的收缩，因此在子宫组织中天然合成的前列腺素类可能是产后子宫收缩乏力的潜在治疗剂，特别是在高血压等情况下。
Prostaglandin (PG) D2, a prostanoid known to have hypotensive effect, can evoke increased in vitro prepartum myometrial contraction resulting from up-regulation of the F prostanoid (FP) receptor. The present study further determined postpartum rat uterine responses to PGD2to evaluate the possibility of the prostanoid becoming a therapeutic for postpartum uterine atony, a major cause of postpartum hemorrhage that can lead to maternal morbidity. In vitro and in vivo postpartum uterine responses to PGD2were determined and compared to those of prepartum rats. Here we show that in postpartum myometrial strips PGD2did evoke a contraction sensitive to FP receptor antagonism. Interestingly, this response was not only to a greater extent than that of prepartum rats, but also comparable with the contraction obtained with PGF2α, a therapeutic for postpartum uterine atony but contradicted in conditions including hypertension. Indeed, PGD2was also found to cause increases of basal uterine contraction under in vivo conditions. Western blots revealed that the expression of FP receptors in postpartum myometrium was higher than that of prepartum rats. Moreover, we noted that the amount of PGD2produced in postpartum uteri, although lower than that of prepartum rats, was increased compared to non-pregnant conditions. These results thus demonstrate that due to a further up-regulation or high expression of myometrial FP receptors, PGD2can evoke potent uterine contraction postpartum, and hence the prostanoid, which is naturally synthesized in uterine tissues, could be a potential therapeutic for postpartum uterine atony, especially in settings, such as hypertension.