Zhang Ying, Li Xiang, Liu Li-Ping, Hong Lan, Liu Xia, Zhang Bo, Wu Cheng-Zhe, Cui Xun
Department of Physiology, School of Medicine, Yanbian University, Yanji 133-002, China.
Institue of Clinical Medicine, Yanbian University, Yanji 133-002, China.
Korean J Physiol Pharmacol. 2017 May;21(3):293-300. doi: 10.4196/kjpp.2017.21.3.293. Epub 2017 Apr 21.
Prostaglandin D (PGD) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGD in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether PGD can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. PGD (0.1 to 10 µM) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of PGD on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 (1.0 µM) and AL-8810 (1.0 µM), PGD and prostaglandin F2α (PGF2α) receptor antagonists, respectively. Moreover, PGD clearly upregulated atrial peroxisome proliferator-activated receptor gamma (PPARγ) and the PGD metabolite 15-deoxy-Δ12,14-PGJ (15d-PGJ, 0.1 µM) dramatically increased atrial ANP secretion. Increased ANP secretions induced by PGD and 15d-PGJ were completely blocked by the PPARγ antagonist GW9662 (0.1 µM). PD98059 (10.0 µM) and LY294002 (1.0 µM), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by PGD. These results indicated that PGD stimulated atrial ANP secretion and promoted positive inotropy by activating PPARγ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating PGD-induced atrial ANP secretion.
前列腺素D（PGD）可能对心肌缺血再灌注（I/R）损伤起作用，并在心脏中发挥抗炎作用。尽管有报道称PGD对心房利钠肽（ANP）分泌的调节作用，但其涉及的机制尚不清楚。本研究的目的是探讨PGD是否能调节离体灌注搏动大鼠心房中ANP的分泌及其潜在机制。PGD（0.1至10μM）以剂量依赖性方式显著增加心房ANP分泌，同时伴有正性肌力作用。AH-6809（1.0μM）和AL-8810（1.0μM）分别为PGD和前列腺素F2α（PGF2α）受体拮抗剂，它们可消除PGD对心房ANP分泌和机械动力学的影响。此外，PGD明显上调心房过氧化物酶体增殖物激活受体γ（PPARγ），PGD代谢产物15-脱氧-Δ12,14-前列腺素J（15d-PGJ，0.1μM）显著增加心房ANP分泌。PGD和l5d-PGJ诱导的ANP分泌增加被PPARγ拮抗剂GW9662（0.1μM）完全阻断。丝裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）拮抗剂PD98059（10.0μM）和磷脂酰肌醇-3激酶（PI3K）/蛋白激酶B（Akt）信号拮抗剂LY294002（1.0μM）分别显著减弱PGD引起的心房ANP分泌增加。这些结果表明，PGD通过激活搏动大鼠心房中的PPARγ刺激心房ANP分泌并促进正性肌力作用。MAPK/ERK和PI3K/Akt信号通路均部分参与调节PGD诱导的心房ANP分泌。
