睡眠与高血压代谢风险及靶器官损害相关性的流行病学及表观遗传学研究
发布时间：2018-05-27 23:32
本文选题：午睡 + PSQI ； 参考：《吉林大学》2017年博士论文
【摘要】：第一章午睡与社区人群不同高血压亚型代谢指标及靶器官损害的相关性分析目的:初步探讨我国北方农村社区未经治疗的人群中午睡习惯与不同高血压亚型代谢因素及靶器官损害的相关性。方法:入选对象完成调查问卷、体格检查、血液生化检测以及心脏超声检查。方差分析、卡方检验、回归分析以及相关分析用于比较午睡与高血压亚型代谢指标以及靶器官损害之间的相关性。结果:共有4780人纳入到本次研究分析,分为正常血压、单纯收缩期高血压、单纯舒张期高血压以及混合性高血压。男性SDH午睡组体重指数、甘油三脂及总胆固醇均显著小于非午睡组,正常血压午睡组尿酸水平低于非午睡组,女性IDH午睡组体重指数及甘油三酯均高于非午睡组。午睡习惯在男女各亚组中均未与肾功能障碍相关,老年女性高血压午睡习惯与左心室肥厚明确正相关。女性正常血压组午睡时间与体重指数正相关,女性IDH组甘油三酯与午睡时间正相关。青年女性高血压中午睡时间与左心室肥厚负相关,男性总体高血压人群午睡时间与左心室肥厚正相关。女性SDH组午睡时间与肾功能障碍正相关。结论:午睡在我国北方农村是一种随年龄增长而增加的生活习惯,不同性别、年龄以及高血压亚型间的午睡时间相似。午睡与男性SDH组及女性IDH代谢因素相关性较紧密。午睡与不同高血压亚型的靶器官损害的相关性不一致。第二章睡眠质量及午睡的交互作用与住院高血压代谢指标及靶器官损害的相关性研究目的:在住院高血压患者中分析睡眠质量(PSQI总分及7个亚成分得分)与代谢指标以及靶器官损害的相关性,对比午睡与不同睡眠质量组各代谢指标以及靶器官损害的关联性。方法:共计189人完成信息采集、体格检查、血生化检测、心脏彩超检查及冠脉造影检查并最终纳入研究,根据PSQI总分划分为男性睡眠障碍组(PSQI≥7)、男性非睡眠障碍组(PSQI㩳7),女性睡眠障碍组(PSQI≥7)及女性非睡眠障碍组(PSQI㩳7)。协方差分析、卡方检验、多元线性及二分类回归分析用于PSQI总分、各亚成分、午睡及午睡时长与年龄、代谢指标、肾小球滤过率、左心室质量指数及冠脉狭窄程度的相关性研究结果:体重指数、空腹血糖、甘油三酯、总胆固醇、低密度脂蛋白胆固醇以及高密度脂蛋白胆固醇与睡眠质量无显著相关。女性睡眠时间、睡眠效率与体重指数呈正相关,入睡时间与空腹血糖呈负相关。男女总体人群PSQI总分与肾小球滤过率无相关。女性催眠药物与左心室质量指数呈负相关。男女不同睡眠质量间的冠脉造影总体阳性率、前降支、回旋支以及右冠脉严重狭窄比率均无明显差异。男性无睡眠障碍组单支血管病变比率明显大于有睡眠障碍组。男性不同睡眠质量组体重指数、空腹血糖、甘油三酯、总胆固醇、低密度脂蛋白胆固醇以及高密度脂蛋白胆固醇均与午睡习惯及午睡时间无相关。女性睡眠障碍组午睡人群甘油三酯水平明显高于对照组,高密度脂蛋白低于对照组,非睡眠障碍组午睡时间与空腹血糖及甘油三酯水平呈正相关。男性不同睡眠质量组午睡与肾小球滤过率均无相关。女性非睡眠障碍组午睡与肾小球滤过率正相关。男性非睡眠障碍组午睡与左心室质量指数及冠脉严重病变血管总数负相关。结论睡眠质量差是住院高血压人群常见症状,女性高血压睡眠质量明显差于男性。男女睡眠质量及与代谢指标相关性不显著。PSQI总分与肾小球率过滤及左心室质量指数无相关性,男性冠脉严重受累血管数可能受睡眠质量影响。习惯性午睡可能会加重女性睡眠障碍代谢紊乱,午睡可能与无睡眠障碍人群靶器官损害的改善有关。第三章高血压人群血栓调节蛋白基因启动子区DNA甲基化修饰及基因表达与睡眠质量的相关性研究目的:观察住院高血压人群中血栓调节蛋白(Thrombomodulin,TM)基因启动子区DNA甲基化及基因表达与睡眠质量的相关性。方法:研究样本来自于第二章纳入人群。进一步按照PSQI总分筛选出的最终分组情况为男性睡眠质量差组22人,男性睡眠质量优组25人,女性睡眠质量差组23人,女性睡眠质量优组24人。TM蛋白基因启动子区DNA甲基化水平检测采取亚硫酸盐PCR测序法,Q-PCR实时荧光定量检测用于血TM基因m RNA水平检测,Western blot蛋白免疫印迹检测用于血TM蛋白水平测定。组间各Cp G位点甲基化水平、TM基因m RNA相对表达量以及TM蛋白相对水平组间对比均采用方差分析;组内甲基化水平与PSQI及代谢指标相关性采用线性回归分析;Bivariate相关分析、聚类分析、主成分分析以及因子分析评估各组内各Cp G位点甲基化修饰程度间的相关性。结果:各组内PSQI各亚成分、代谢指标及中淋比与平均DNA甲基化水平无相关性。男性睡眠质量优组Cp G26号位点甲基化水平,女性睡眠质量优组Cp G8号、Cp G13号、Cp G19号及整体DNA甲基化水平高于睡眠质量差组。男性睡眠质量差组中第1、2、3、6、8、10、11、12、16、20和25号位点,睡眠质量优组第3号Cp G位点未检测到甲基化修饰。女性睡眠质量差组存在11个,而睡眠质量优组存在7个位点未检测到甲基化修饰。男女睡眠质量优组中各Cp G位点DNA甲基化水平相关度较高。男性Cp G位点19聚为一类,Cp G3、22、25、26位点聚为一类,Cp G14及Cp G15位点聚为一类,样本1123号(睡眠质量优组)及样本1142号(睡眠质量差组)各自为一类。女性Cp G19为一类,Cp G6及Cp G13为一类,Cp G14与Cp G15为一类,样本2114(睡眠质量优组)与2143(睡眠质量差组)为一类,样本2117、2106、2109、2121、2104、2112及2101(均来自于睡眠质量优组)为一类。男性睡眠质量差组主成分一包含Cp G7、23、24及9,主成分二包含Cp G14、15及5,主成分三包含Cp G17及18,主成分四包含Cp G13和4,主成分五包含Cp G26;男性睡眠质量优组主成分一包含Cp G16、18、1、20、12、8、5、11、13、9、17、24、4、15、21、6、7、10、2以及14,主成分二则包含Cp G19及22,主成分三只包含Cp G22。女性睡眠质量差组与睡眠质量优组主成分分别为6个及7个,每个主成分包含的Cp G位点数量为3至4个。男女睡眠质量差组m RNA相对表达量及TM蛋白水平均高于睡眠质量优组。结论:TM基因启动子区DNA甲基化水平总体上与代谢指标及中淋比无关。高血压人群不同睡眠质量组间的TM基因启动子区Cp G位点DNA甲基化水平,甲基化修饰分布范围及各位点DNA甲基化关联特点的明显差异可能与TM蛋白的基因表达调控明确相关。
[Abstract]:In the first chapter, the correlation between the metabolic indices of hypertension subtypes and the damage of target organs of different hypertensive subtypes in the community population was analyzed. The correlation between the noon sleep habits and the metabolic factors of different hypertensive subtypes and target organ damage in the untreated population of the rural communities in the north of China was preliminarily discussed. Biochemical tests and echocardiography, variance analysis, chi square test, regression analysis, and correlation analysis were used to compare the correlation between the metabolic indices of nap and hypertension subtypes and target organ damage. Results: a total of 4780 people were included in this study, divided into normal blood pressure, simple systolic hypertension, and simple diastolic blood. The body mass index, three fat and total cholesterol in the male SDH nap group were significantly lower than those in the non nap group, and the normal blood pressure nap group was lower than the non nap group, and the body mass index and triglyceride in the IDH nap group were higher than those in the non nap group. The nap time of the elderly women was positively correlated with the left ventricular hypertrophy. The nap time in the female normal blood pressure group was positively correlated with the body mass index, and the triglyceride in the female IDH group was positively correlated with the nap time. The midday sleep time of the young women was negatively correlated with the left ventricular hypertrophy, and the midday nap time and the left ventricular hypertrophy were positive in the male population. The nap time in the female SDH group was positively related to the renal dysfunction. Conclusion: the nap in the northern rural areas of China is a lifestyle that increases with age. The nap time of different sex, age and hypertension subtype is similar. The nap is closely related to the male SDH group and the female IDH Xie Yin. The correlation between the second chapters of sleep quality and nap interaction with the metabolic indexes of hypertension and target organ damage in hospitalized hypertension patients: the correlation between the quality of sleep (PSQI total score and the score of 7 subcomponents) and the metabolic index and target organ damage in hospitalized hypertensive patients. Methods: 189 people completed information collection, physical examination, blood biochemical test, cardiac color Doppler examination and coronary angiography, and finally included the study. According to the PSQI total score, the male sleep barrier group (PSQI > 7), the male non sleep disorder group (PSQI? 7), women were divided into the male sleep disorder group (PSQI? 7), Sexual sleep disorder group (PSQI > 7) and female non sleep disorder group (PSQI? 7). Covariance analysis, chi square test, multivariate linear and two classification regression analysis used for PSQI total score, subcomponents, nap and nap length and age, metabolic index, glomerular filtration rate, left ventricular mass index and coronary stenosis degree: weight index There was no significant correlation between fasting blood glucose, triglyceride, triglyceride, total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol. There was a positive correlation between sleep time, sleep efficiency and body mass index, and a negative correlation between sleep time and fasting blood glucose. There was no correlation between PSQI total score and glomerular filtration rate in men and women. There was a negative correlation between the hypnotic drugs and the left ventricular mass index. There was no significant difference in the overall positive rate of coronary angiography between men and women, the anterior descending branch, the circumflex branch, and the right coronary stenosis. The rate of single vessel lesion in the male non sleep disorder group was significantly greater than that in the sleep barrier group. Fasting blood glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol and high density lipoprotein cholesterol were not related to nap habit and nap time. The level of triglyceride in the nap group of female sleep disorder group was significantly higher than that of the control group, and the high density lipoprotein was lower than the control group. The nap time and fasting blood glucose in the non sleep disorder group were compared with the control group. The level of triglyceride was positively correlated with the level of triglyceride. There was no correlation between nap and glomerular filtration rate in men with different sleep quality groups. The nap in the female non sleep disorder group was positively correlated with the glomerular filtration rate. The nap in the male non sleep disorder group was negatively correlated with the left ventricular mass index and the total number of coronary artery disease. The sleep quality of women with hypertension is significantly worse than that in men. There is no significant correlation between the quality of sleep and the correlation with metabolic indicators. There is no correlation between the total score of.PSQI and the filtration of glomerular rate and the left ventricular mass index. The number of heavily affected vessels in male coronary arteries may be affected by the quality of sleep. Metabolic disorder, nap may be related to the improvement of target organ damage in people with no sleep disorder. Third the correlation between DNA methylation and gene expression of thromboxane gene promoter region in hypertensive population and the correlation between gene expression and sleep quality: To observe the DNA promoter region DNA in the hospitalized hypertensive population. Methods: the correlation between methylation and gene expression and quality of sleep. Methods: the study samples were included in the second chapters. The final grouping of male sleep quality was 22 people, 25 male sleep quality group, 23 female sleep poor group and 24.TM protein gene in female sleep quality group. The level of DNA methylation was detected by PCR sequencing, and Q-PCR real-time quantitative detection was used to detect the level of M RNA in blood TM gene. Western blot protein immunoblotting was used to determine the level of TM protein. The level of methylation of Cp G loci, the relative expression of TM genes and the relative levels of the proteins were all compared. The correlation between the level of intra group methylation and PSQI and metabolic indexes was analyzed by linear regression analysis; Bivariate correlation analysis, cluster analysis, principal component analysis and factor analysis were used to evaluate the correlation between the degree of methylation modification of Cp G loci in each group. Results: the subcomponents of PSQI, metabolic indices and the ratio of PSQI to the mean DNA in each group Methylation level was not related. The level of methylation at Cp G26 locus in male sleep quality group, Cp G8, Cp G13, Cp G19 and whole DNA methylation in female sleep quality group were higher than that in poor sleep quality group. The number of 1,2,3,6,8,10,11,12,16,20 and 25 in the male sleep quality poor group, and the quality of sleep quality group third Cp G loci were not examined. Methylation modification. There were 11 women with poor quality of sleep, while there were 7 sites in the superior sleep quality group that did not detect methylation. The Cp G locus DNA methylation level was higher in male and female superior sleep quality groups. Male Cp G site 19 was one class, Cp G3,22,25,26 loci were one class, Cp G14 and Cp G15 loci were a class. The number 1123 (sleep quality excellent group) and sample 1142 (poor sleep quality group) are one class respectively. Female Cp G19 is a class, Cp G6 and Cp G13 are a class, Cp G14 and Cp G15 are a class, samples 2114 (sleep quality excellent group) and 2143 (sleep poor group) are a class, sample 211721062109212121042112 and 2101 (all from the sleep quality excellent group) The principal component of the poor male sleep quality group includes Cp G7,23,24 and 9, principal component two contains Cp G14,15 and 5, principal component three contains Cp G17 and 18, principal component four contains Cp G13 and 4, and principal component five contains Cp G26; male sleep quality dominant components include Cp G16,18,1,20,12,8,5,11,13,9,17,24,4,15,21,6,7,10,2 and 14, and two principal components. Two Including Cp G19 and 22, the principal component three only contains Cp G22. female sleep quality poor group and the sleep quality excellent group principal component respectively 6 and 7, each principal component contains the Cp G bit number is 3 to 4. The male and female sleep quality poor group M RNA relative expression and the TM protein level are higher than the sleep quality superior group. Conclusion: TM gene promoter region DNA methyl The level of Cp G locus DNA methylation in the promoter region of TM gene in different sleep quality groups, the distribution of methylation modification and the significant difference in the correlation between DNA methylation of each point may be clearly related to the regulation of the gene expression of TM protein.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R544.1
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本文编号：1944262
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