环境气候地域因素对南疆维汉民族方域性病证罹患特征及心血管衰老规律差异影响的分子调控机制研究

Cardiovascular disease is a complex disease which is effected by environmental, regional and genetic factors, the threshold of disease occurrence and the severity of various kinds of cardiovascular were changed by cardiovascular aging. the Xinjiang regional special syndrome—Northwest dryness syndrome(NDS)，which is caused by Dryness pathogen, is the common disease state of the health of the residents of all ethnic groups in Xinjiang and the northwest of China. According to the earlier research results, the northwest dryness syndrome(NDS)，Xinjiang regional special symptoms, is correlated to the cardiovascular aging mechanism. The northwest dryness syndrome(NDS) has a significant influence on cardiovascular aging process of Uygur and Han people. So except for the environmental and regional factors, Does the specificity of gene level of people in different nationalities cause the differences of the attact rate of the northwest dryness syndrome(NDS) and the regularity of cardiovascular aging?. The study is developed on the reality of prevention of cardiovascular aging of Uygur and Han people in the dry desert environment of south Xinjiang, using methods of metrology, traditional literature research and mathematical statistics etc, combining of microscopical means of modern medicine and macroscopical means of traditional chinese medicine, screening out cardiovascular aging biomarkers, from epidemiology, prevention and treatment of cardiovascular disease, combining the results of Northwest Dryness Syndrome (NDS). The research is to study on the genetic basis of regularity of temporal changes for cardiovascular aging in Uygur and Han people in south Xinjiang. The study is to discuss the molecular regulatory mechanism of epidemiological characteristics of the Xinjiang regional special syndrome and difference of regularity of cardiovascular aging of Uygur and Han in south Xinjiang by effect of special regional climate characteristic. On the basis of investigation of people, we use the method of detection of miRNA expression profiling chip and the qRT-PCR to verify the result of the chip, then discuss the possible gene regulation mechanism of cardiovascular aging at the molecular level, offering potential molecular targets for anti-cardiovascular aging effectively. And the research is to provide the new ideas and methods for the prevention of cardiovascular aging and cardiovascular disease in this region.

心血管病是多种环境地域和遗传因素共同作用的复杂性状疾病，心血管衰老改变了各种心血管病发生阈值和严重程度。燥邪引发的新疆方域性病证—西北燥证是影响新疆各族居民身体健康的共同病证状态。前期研究成果显示，西北燥证与心血管衰老机制之间存在相关，西北燥证是影响维汉民族心血管衰老进程的加重因素之一。除环境气候地域因素，不同民族基因水平的特异性是否导致南疆维汉民族方域性病证罹患特征和心血管衰老规律的差异？本项目拟从南疆沙漠干燥地域环境下，最具代表性的南疆维汉民族心血管衰老防治实际出发，结合西北燥证既往研究成果，采用计量辨证、中医传统理论、数理统计学及分子生物学方法，研究南疆维汉民族心血管衰老规律差异影响的遗传学基础，在人群调查研究的基础上，从分子水平探讨环境气候地域因素对南疆维汉民族方域性病证罹患特征及心血管衰老规律差异影响的分子调控机制，为心血管衰老及心血管病防治提供真实世界的研究证据及潜在分子靶点。

心血管疾病为环境地域及遗传因素共同作用的复杂性状疾病，心血管衰老改变了各种心血管病发生阈值和严重程度，显著增加心血管疾病的发病率。西北燥证是影响新疆地区各族居民身体健康的共同病证状态，与心血管衰老机制之间存在相关，是影响心血管衰老进程加重因素之一。本项目拟从新疆地区心血管衰老防治实际出发，结合既往研究成果，采用计量辨证方法、中医传统理论方法、数理统计学方法及分子生物学方法，研究南疆地区维汉民族心血管衰老规律差异的遗传学基础，探讨新疆地区西北燥证与心血管衰老规律差异及其miRNAs调控机制之间的相关关系。研究资料分析显示：①心血管衰老相关指标中，SBP、DBP、PP、PPI、GLU、TC、BUN、Cys-C等指标均随增龄呈上升趋势，HDL-C、LVEF、PSV 等指标均随增龄呈下降趋势。②南疆地区维汉民族西北燥证罹患率随增龄呈现上升趋势，且维族西北燥证心血管衰老程度略重于汉族。③南疆地区不同人群IMT、UA、GLU、hs-CRP等指标与西北燥证总积分存在相关性，提示西北燥证与心血管衰老之间具有明确相关性。④南疆地区不同人群虚证罹患率从高到低依次为心虚证、气虚证、肝虚证、肾虚证、阳虚证、阴虚证、血虚证、脾虚证、肺虚证、胃虚证；而其中阳虚证、心虚证、肝虚证、肾虚证罹患率随增龄逐渐升高，其中肾虚证与心血管衰老密切相关。⑤sa-miR-21-3p、hsa-miR-212-3p、hsa-miR-338-5p是南疆地区不同人群心血管衰老时序变化相关差异miRNA，可能通过调控靶基因PTEN和SIRT1的表达，从而影响心血管衰老。⑥TNF-α、IL-2与西北燥证罹患情况及心血管衰老时序变化呈正相关，FOXO1、VEGF与西北燥证罹患情况及心血管衰老时序变化呈负相关，eNOS与西北燥证罹患情况无明显相关性，但与心血管衰老时序变化呈负相关。研究结果证明：新疆特殊地理气候特点对不同人群心血管衰老进程及规律存在影响，西北燥证与心血管衰老机制之间存在相关关系，新疆地区不同人群的心血管衰老相关miRNAs调控基因存在差异表达，可能通过SIRT1通路调控心血管衰老进程，这为本地区心血管衰老及心血管疾病的防治提供新的思路和方法。