State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China;
Am J Physiol Heart Circ Physiol. 2014 Apr 15;306(8):H1105-15. doi: 10.1152/ajpheart.00645.2013. Epub 2014 Feb 14.
Several medical conditions exhibit age- and sex-based differences. Whether or not traumatic shock exhibits such differences with regard to vascular responsiveness is not clear. In a cohort of 177 healthy subjects and 842 trauma patients (21-82 years) as well as different ages (4, 8, 10, 14, 18, and 24 wk; 1 and 1.5 years) and sexes of Sprague-Dawley normal and traumatic shock rats, the age- and sex-based differences of vascular responsiveness and the underlying mechanisms were investigated. Middle-aged and young women as well as female rats of reproductive age had higher vascular responsiveness in the normal condition and a lower decrease in vascular responsiveness after traumatic shock than older men and male rats of identical age. Exogenous supplementation of 17β-estrdiol increased vascular reactivity in both male and femal rats of 8-24 wk and preserved vascular responsiveness in rats following traumatic shock. No effect was observed in rats 1 to 1.5 years. These protective effects of estrogen were closely related to G protein-coupled receptor (GPR)30, estrogen receptor-mediated Rho kinase, and PKC pathway activation. Vascular responsiveness exhibits age- and sex-based differences in healthy subjects and trauma patients. Estrogen and its receptor (GPR30) mediated activation of Rho kinase and PKC using genomic and nongenomic mechanisms to elicit protective effects in vascular responsiveness. This finding is important for the personalized treatment for several age- and sex-related diseases involving estrogen.
几种医学病症表现出与年龄和性别相关的差异。创伤性休克是否在血管反应性方面表现出这种差异尚不清楚。在一个由 177 名健康受试者和 842 名创伤患者（21-82 岁）以及不同年龄（4、8、10、14、18 和 24 周；1 和 1.5 岁）和性别（Sprague-Dawley 正常和创伤性休克大鼠）组成的队列中，研究了血管反应性的年龄和性别差异及其潜在机制。中年和年轻女性以及处于生殖期的雌性大鼠在正常情况下具有更高的血管反应性，而在创伤性休克后血管反应性的下降幅度较低。外源性补充 17β-雌二醇可增加 8-24 周龄雄性和雌性大鼠的血管反应性，并可维持创伤性休克后大鼠的血管反应性。在 1 至 1.5 岁的大鼠中未观察到这种作用。雌激素的这些保护作用与 G 蛋白偶联受体（GPR）30、雌激素受体介导的 Rho 激酶和 PKC 通路激活密切相关。血管反应性在健康受试者和创伤患者中表现出与年龄和性别相关的差异。雌激素及其受体（GPR30）通过基因组和非基因组机制激活 Rho 激酶和 PKC，从而在血管反应性中产生保护作用。这一发现对于涉及雌激素的几种与年龄和性别相关的疾病的个体化治疗非常重要。
