PDF(Pubmed)
Abstract：
UNASSIGNED: The role of phosphodiesterase 5 (Pde5) in obstructive sleep apnea-induced damage remains unclear. Our study aimed to investigate the role of Pde5 in the chronic intermittent hypoxia (CIH) model. C57BL/6J wild-type (WT) mice (n = 48) and Pde5 knockout (Pde5 -/- ) mice (n = 24) were randomly assigned to CIH group and room air group. After 6 weeks, some WT mice (n = 24) in CIH group were given sildenafil or saline gavage for another 4 weeks. Blood pressure was regularly measured during the experiment. Echocardiography was used to estimate cardiac function. We collected organs from each group of mice and measured their physical indicators. Histochemical staining was used to explore the size of cardiomyocyte and fibrosis area of various organs. Cyclic guanosine monophosphate and malondialdehyde concentrations in serum were measured by ELISA assay. Compared with the RA-treated group, the 6-week CIH resulted in a significant increase in blood pressure, altered heart structure, and reduced serum cyclic guanosine monophosphate in WT mice. Pde5 -/- mice and sildenafil intragastric administration significantly reduced systolic blood pressure in CIH condition and attenuated the damage of target organs. In CIH model, we found that the cardiomyocyte size and fibrosis area of heart and kidney significantly reduced in Pde5 -/- groups. Besides, endogenous and exogenous inhibition of Pde5 reduced malondialdehyde level and inflammatory and oxidative stress markers expression in CIH condition. In this study, we found that Pde5 inhibition could reduce blood pressure and alleviate target organ damage in the CIH model, which may be mediated through the oxidative stress pathway.
摘要：
■磷酸二酯酶5（Pde5）在阻塞性睡眠呼吸暂停（OSA）引起的损伤中的作用尚不清楚。我们的研究旨在探讨Pde5在慢性间歇性缺氧（CIH）模型中的作用。将C57BL/6J野生型（WT）小鼠（n=48）和Pde5基因敲除（Pde5-/-）小鼠（n=24）随机分为CIH组和室内空气（RA）组。6周后,CIH组的部分WT小鼠(n=24)再给予西地那非或生理盐水灌胃4周.在实验期间定期测量血压。超声心动图用于评估心功能。我们从每组小鼠中收集器官并测量其物理指标。组织化学染色用于探索心肌细胞的大小和各种器官的纤维化面积。采用ELISA法检测血清环磷酸鸟苷(cGMP)和丙二醛(MDA)浓度。与RA治疗组相比，6周CIH导致血压显著升高，WT小鼠心脏结构改变和血清cGMP降低。Pde5-/-小鼠和西地那非灌胃可显著降低CIH条件下的收缩压，减轻靶器官的损伤。InCIH模型,我们发现Pde5-/-组的心肌细胞大小和心脏和肾脏的纤维化面积显着减少。此外,内源性和外源性抑制Pde5降低了CIH条件下的MDA水平以及炎症和氧化应激标志物的表达。在本研究中,我们发现在CIH模型中抑制Pde5可以降低血压和减轻靶器官损伤,这可能是通过氧化应激途径介导的。
