Behavioral Medicine Research Center and Department of Psychology, University of Miami, Coral Gables, FL 33124, United States.
Psychoneuroendocrinology. 2013 May;38(5):685-93. doi: 10.1016/j.psyneuen.2012.08.009. Epub 2012 Sep 19.
Oxytocin (OT) is a neurohypophyseal peptide traditionally associated with female reproductive functioning, and more recently with prosocial behavior. OT and its receptor are also expressed in the heart and vascular tissue and play a role in cardiovascular homeostasis. In vitro, it has been demonstrated that OT decreases NADPH-dependent superoxide production and pro-inflammatory cytokine release from vascular endothelial cells and macrophages, suggesting that OT may attenuate pathophysiological processes involved with atherosclerotic lesion formation. The present study sought to determine the effect of chronic exogenous OT administration on inflammation and atherosclerosis in an animal model of dyslipidemia and atherosclerosis, the Watanabe Heritable Hyperlipidemic (WHHL) rabbit. Twenty-two, 3-month-old WHHLs were surgically implanted with osmotic mini-pumps containing OT (n=11) or vehicle (n=11), and then were individually housed for the entire study. Blood and 24-h urine samples were taken at baseline and after 8 (midpoint) and 16 (endpoint) weeks of treatment. At endpoint, the aortas and visceral fat samples were dissected and stored for analyses. There were no group differences in body weight, serum lipids, plasma/urinary measures of oxidative stress, plasma cortisol or urinary catecholamines over the 16-week treatment. OT-treated animals exhibited significantly lower plasma C-reactive protein levels at midpoint and endpoint and developed significantly less atherosclerosis in the thoracic aorta relative to vehicle control animals at endpoint (p<0.05). Cytokine gene expression from visceral adipose tissue samples suggested that there was a decrease in adipose tissue inflammation in the OT-treated group compared to the vehicle control group, however these differences were not statistically significant. These results suggest that chronic peripheral OT administration can inhibit inflammation and atherosclerotic lesion development.
催产素（OT）是一种传统上与女性生殖功能相关的神经垂体肽，最近也与亲社会行为相关。OT 及其受体也在心脏和血管组织中表达，并在心血管稳态中发挥作用。在体外，已经证明 OT 可减少血管内皮细胞和巨噬细胞中 NADPH 依赖性超氧化物产生和促炎细胞因子释放，这表明 OT 可能减轻与动脉粥样硬化病变形成相关的病理生理过程。本研究旨在确定慢性外源性 OT 给药对血脂异常和动脉粥样硬化动物模型，即 Watanabe 遗传性高脂血症（WHHL）兔的炎症和动脉粥样硬化的影响。22 只 3 月龄的 WHHL 兔接受手术植入含有 OT（n=11）或载体（n=11）的渗透微型泵，然后单独饲养整个研究过程。在基线、8 周（中点）和 16 周（终点）治疗后采集血液和 24 小时尿液样本。在终点时，解剖并储存主动脉和内脏脂肪样本以进行分析。在 16 周的治疗过程中，两组动物的体重、血清脂质、血浆/尿液氧化应激测量值、血浆皮质醇或尿液儿茶酚胺均无差异。与载体对照组相比，OT 治疗组在中点和终点时的血浆 C 反应蛋白水平显著降低，在终点时胸主动脉中的动脉粥样硬化程度显著降低（p<0.05）。来自内脏脂肪组织样本的细胞因子基因表达表明，与载体对照组相比，OT 治疗组的脂肪组织炎症减少，但这些差异无统计学意义。这些结果表明，慢性外周 OT 给药可抑制炎症和动脉粥样硬化病变的发展。
