不同青春发动时相青少年血压变化特点及其性激素对血压调节作用的研究

Adolescent high blood pressure is closely related with adulthood hypertension. Our previous studies have shown that there are phase and gender differences in blood pressure changes during puberty. It has been reported that sex hormones have an effect on hypertension among adults, but the mechanism of how adolescent sex hormones regulate blood pressure is still unclear. In addition, cohort study on the relationship between sex hormones and blood pressure during puberty has not been reported yet. Therefore, we will firstly integrate the data of Chinese National Survey on Students’ Constitution and Health in 2005, 2010 and 2014 to analyze the changes of blood pressure in different developmental phases of puberty. Secondly, we will carry out the baseline survey of about 4,000 students from primary and secondary schools in Zhongshan city, exploring the distribution of levels of sex hormones in the different timing of puberty onset and the relationship between sex hormones and blood pressure. Finally, we will establish a study cohort of adolescent blood pressure based on the baseline survey, screening students who have not entered the Tanner Ⅱ stage as the sample of the study including girls aged 9 to 11 years and boys aged 11 to 13 years. In the cohort study, we will monitor height, weight and blood pressure every six months while secondary sex characteristics will be examined and saliva and blood samples will be collected every year. We will follow up the cohort consecutively for 3 years, dynamically monitoring and observing the changes of sex hormones in different puberty onset phases and the relationship between the increase of sex hormone and blood pressure change, to further validate the effect of sex hormones on regulating blood pressure through vascular factors, which will provide new evidence for early prevention and control of adulthood hypertension.

青春期血压偏高与成年期高血压密切相关，课题组前期研究显示青春期血压变化存在时相差异和性别差异。研究显示成年人性激素与血压关系密切，但青春期性激素水平骤升是否影响血压调节及如何调节尚不明确，关于青少年性激素与血压的队列研究未见报道。本研究整合2005年至2014年全国学生体质与健康调研数据，分析我国青少年不同发育时期血压的变化特点；然后对中山市约4000名中小学生开展基线调查，比较不同青春发动时相性激素水平的分布规律及其与血压的关系；最后在基线调查基础上，筛选尚未进入Tanner Ⅱ期的9～11岁女生和11～13岁男生，建立青春期血压研究队列，每6个月监测一次身高、体重和血压，每年进行第二性征检查，并收集唾液和静脉血样；连续随访3年，动态监测、观察不同青春发动时相性激素水平及骤升幅度与血压改变的关系，验证性激素对血压的调节作用及其与血管因子的关联，为高血压早期防控提供新的思路和依据。

【背景】青春期是生长发育的重要时期，其重要特征是各种激素分泌的急剧增加、生物学功能空前活跃。青春期血压偏高检出率较高，并显著增加成年期发生高血压的风险。青春期性激素分泌明显增加，对血压调节产生重要影响。.【研究内容】探索我国青春期血压变化特点及血压偏高流行情况，不同青春期发育阶段儿童血压水平变化特点，青春期启动与青春期血压升高的潜在机制及性激素在血压升高过程中的调节作用。探索青春期高血压的潜在发生机制及与青春期高血压发生相关的基因。.【结果】本国儿童青少年血压水平和血压偏高检出率存在明显的地域性、年龄段和性别差异，具体表现为东部和沿海地区高、中西部地区低；生长突增期高、生长突增前期和后期低；男生以高收缩压为主、女生以高舒张压为主。本研究结果发现，BMI、腰围身高比、皮褶厚度等反应个体肥胖程度的指标均与血压水平和血压偏高风险具有显著关联，其中反映腹型肥胖的指标，如腰围 、腰围升高比等，对血压的影响作用更大。从长期角度来看，经济发展和肥胖患病率的升高与青少年高血压患病率的提高呈现显著联系。男女生青春期启动时间存在显著的性别差异，且青春发动时相与个体BMI水平、睡眠时长、家庭经济水平等因素均相关。在同一年龄中，青春期已经启动的儿童以及青春发动时相较早儿童有血压水平和血压偏高检出率均相对较高。机制方面研究结果显示，胰岛素诱导基因rs10185316与儿童青少年的舒张压、脉压差存在显著关联，其作用独立于BMI。固醇调控元件结合蛋白裂解激活蛋白（SCAP）对于血压的影响支持了高血压的遗传学说，同时rs12487736基因在其中发挥着重要作用。.【关键数据】本研究最终形成厦门市青春期高血压队列数据库，该数据库对研究青春期高血压的影响因素、变化规律、潜在机制具有重大价值。.【科学意义】通过年龄、性别、身高、体重、性激素水平和血管因子水平建立青春期高血压风险模型，对青春期血压变化的轨迹具有一定的预测作用。同时确定了我国目前青春期高血压的流行现状和分布特点，为制定相应的防控措施提供了理论依据和支持。