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睡眠與高血壓代謝風(fēng)險(xiǎn)及靶器官損害相關(guān)性的流行病學(xué)及表觀遺傳學(xué)研究

發(fā)布時(shí)間:2018-05-27 23:32

  本文選題:午睡 + PSQI ; 參考:《吉林大學(xué)》2017年博士論文


【摘要】:第一章午睡與社區(qū)人群不同高血壓亞型代謝指標(biāo)及靶器官損害的相關(guān)性分析目的:初步探討我國(guó)北方農(nóng)村社區(qū)未經(jīng)治療的人群中午睡習(xí)慣與不同高血壓亞型代謝因素及靶器官損害的相關(guān)性。方法:入選對(duì)象完成調(diào)查問(wèn)卷、體格檢查、血液生化檢測(cè)以及心臟超聲檢查。方差分析、卡方檢驗(yàn)、回歸分析以及相關(guān)分析用于比較午睡與高血壓亞型代謝指標(biāo)以及靶器官損害之間的相關(guān)性。結(jié)果:共有4780人納入到本次研究分析,分為正常血壓、單純收縮期高血壓、單純舒張期高血壓以及混合性高血壓。男性SDH午睡組體重指數(shù)、甘油三脂及總膽固醇均顯著小于非午睡組,正常血壓午睡組尿酸水平低于非午睡組,女性IDH午睡組體重指數(shù)及甘油三酯均高于非午睡組。午睡習(xí)慣在男女各亞組中均未與腎功能障礙相關(guān),老年女性高血壓午睡習(xí)慣與左心室肥厚明確正相關(guān)。女性正常血壓組午睡時(shí)間與體重指數(shù)正相關(guān),女性IDH組甘油三酯與午睡時(shí)間正相關(guān)。青年女性高血壓中午睡時(shí)間與左心室肥厚負(fù)相關(guān),男性總體高血壓人群午睡時(shí)間與左心室肥厚正相關(guān)。女性SDH組午睡時(shí)間與腎功能障礙正相關(guān)。結(jié)論:午睡在我國(guó)北方農(nóng)村是一種隨年齡增長(zhǎng)而增加的生活習(xí)慣,不同性別、年齡以及高血壓亞型間的午睡時(shí)間相似。午睡與男性SDH組及女性IDH代謝因素相關(guān)性較緊密。午睡與不同高血壓亞型的靶器官損害的相關(guān)性不一致。第二章睡眠質(zhì)量及午睡的交互作用與住院高血壓代謝指標(biāo)及靶器官損害的相關(guān)性研究目的:在住院高血壓患者中分析睡眠質(zhì)量(PSQI總分及7個(gè)亞成分得分)與代謝指標(biāo)以及靶器官損害的相關(guān)性,對(duì)比午睡與不同睡眠質(zhì)量組各代謝指標(biāo)以及靶器官損害的關(guān)聯(lián)性。方法:共計(jì)189人完成信息采集、體格檢查、血生化檢測(cè)、心臟彩超檢查及冠脈造影檢查并最終納入研究,根據(jù)PSQI總分劃分為男性睡眠障礙組(PSQI≥7)、男性非睡眠障礙組(PSQI㩳7),女性睡眠障礙組(PSQI≥7)及女性非睡眠障礙組(PSQI㩳7)。協(xié)方差分析、卡方檢驗(yàn)、多元線性及二分類(lèi)回歸分析用于PSQI總分、各亞成分、午睡及午睡時(shí)長(zhǎng)與年齡、代謝指標(biāo)、腎小球?yàn)V過(guò)率、左心室質(zhì)量指數(shù)及冠脈狹窄程度的相關(guān)性研究結(jié)果:體重指數(shù)、空腹血糖、甘油三酯、總膽固醇、低密度脂蛋白膽固醇以及高密度脂蛋白膽固醇與睡眠質(zhì)量無(wú)顯著相關(guān)。女性睡眠時(shí)間、睡眠效率與體重指數(shù)呈正相關(guān),入睡時(shí)間與空腹血糖呈負(fù)相關(guān)。男女總體人群PSQI總分與腎小球?yàn)V過(guò)率無(wú)相關(guān)。女性催眠藥物與左心室質(zhì)量指數(shù)呈負(fù)相關(guān)。男女不同睡眠質(zhì)量間的冠脈造影總體陽(yáng)性率、前降支、回旋支以及右冠脈嚴(yán)重狹窄比率均無(wú)明顯差異。男性無(wú)睡眠障礙組單支血管病變比率明顯大于有睡眠障礙組。男性不同睡眠質(zhì)量組體重指數(shù)、空腹血糖、甘油三酯、總膽固醇、低密度脂蛋白膽固醇以及高密度脂蛋白膽固醇均與午睡習(xí)慣及午睡時(shí)間無(wú)相關(guān)。女性睡眠障礙組午睡人群甘油三酯水平明顯高于對(duì)照組,高密度脂蛋白低于對(duì)照組,非睡眠障礙組午睡時(shí)間與空腹血糖及甘油三酯水平呈正相關(guān)。男性不同睡眠質(zhì)量組午睡與腎小球?yàn)V過(guò)率均無(wú)相關(guān)。女性非睡眠障礙組午睡與腎小球?yàn)V過(guò)率正相關(guān)。男性非睡眠障礙組午睡與左心室質(zhì)量指數(shù)及冠脈嚴(yán)重病變血管總數(shù)負(fù)相關(guān)。結(jié)論睡眠質(zhì)量差是住院高血壓人群常見(jiàn)癥狀,女性高血壓睡眠質(zhì)量明顯差于男性。男女睡眠質(zhì)量及與代謝指標(biāo)相關(guān)性不顯著。PSQI總分與腎小球率過(guò)濾及左心室質(zhì)量指數(shù)無(wú)相關(guān)性,男性冠脈嚴(yán)重受累血管數(shù)可能受睡眠質(zhì)量影響。習(xí)慣性午睡可能會(huì)加重女性睡眠障礙代謝紊亂,午睡可能與無(wú)睡眠障礙人群靶器官損害的改善有關(guān)。第三章高血壓人群血栓調(diào)節(jié)蛋白基因啟動(dòng)子區(qū)DNA甲基化修飾及基因表達(dá)與睡眠質(zhì)量的相關(guān)性研究目的:觀察住院高血壓人群中血栓調(diào)節(jié)蛋白(Thrombomodulin,TM)基因啟動(dòng)子區(qū)DNA甲基化及基因表達(dá)與睡眠質(zhì)量的相關(guān)性。方法:研究樣本來(lái)自于第二章納入人群。進(jìn)一步按照PSQI總分篩選出的最終分組情況為男性睡眠質(zhì)量差組22人,男性睡眠質(zhì)量?jī)?yōu)組25人,女性睡眠質(zhì)量差組23人,女性睡眠質(zhì)量?jī)?yōu)組24人。TM蛋白基因啟動(dòng)子區(qū)DNA甲基化水平檢測(cè)采取亞硫酸鹽PCR測(cè)序法,Q-PCR實(shí)時(shí)熒光定量檢測(cè)用于血TM基因m RNA水平檢測(cè),Western blot蛋白免疫印跡檢測(cè)用于血TM蛋白水平測(cè)定。組間各Cp G位點(diǎn)甲基化水平、TM基因m RNA相對(duì)表達(dá)量以及TM蛋白相對(duì)水平組間對(duì)比均采用方差分析;組內(nèi)甲基化水平與PSQI及代謝指標(biāo)相關(guān)性采用線性回歸分析;Bivariate相關(guān)分析、聚類(lèi)分析、主成分分析以及因子分析評(píng)估各組內(nèi)各Cp G位點(diǎn)甲基化修飾程度間的相關(guān)性。結(jié)果:各組內(nèi)PSQI各亞成分、代謝指標(biāo)及中淋比與平均DNA甲基化水平無(wú)相關(guān)性。男性睡眠質(zhì)量?jī)?yōu)組Cp G26號(hào)位點(diǎn)甲基化水平,女性睡眠質(zhì)量?jī)?yōu)組Cp G8號(hào)、Cp G13號(hào)、Cp G19號(hào)及整體DNA甲基化水平高于睡眠質(zhì)量差組。男性睡眠質(zhì)量差組中第1、2、3、6、8、10、11、12、16、20和25號(hào)位點(diǎn),睡眠質(zhì)量?jī)?yōu)組第3號(hào)Cp G位點(diǎn)未檢測(cè)到甲基化修飾。女性睡眠質(zhì)量差組存在11個(gè),而睡眠質(zhì)量?jī)?yōu)組存在7個(gè)位點(diǎn)未檢測(cè)到甲基化修飾。男女睡眠質(zhì)量?jī)?yōu)組中各Cp G位點(diǎn)DNA甲基化水平相關(guān)度較高。男性Cp G位點(diǎn)19聚為一類(lèi),Cp G3、22、25、26位點(diǎn)聚為一類(lèi),Cp G14及Cp G15位點(diǎn)聚為一類(lèi),樣本1123號(hào)(睡眠質(zhì)量?jī)?yōu)組)及樣本1142號(hào)(睡眠質(zhì)量差組)各自為一類(lèi)。女性Cp G19為一類(lèi),Cp G6及Cp G13為一類(lèi),Cp G14與Cp G15為一類(lèi),樣本2114(睡眠質(zhì)量?jī)?yōu)組)與2143(睡眠質(zhì)量差組)為一類(lèi),樣本2117、2106、2109、2121、2104、2112及2101(均來(lái)自于睡眠質(zhì)量?jī)?yōu)組)為一類(lèi)。男性睡眠質(zhì)量差組主成分一包含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;男性睡眠質(zhì)量?jī)?yōu)組主成分一包含Cp G16、18、1、20、12、8、5、11、13、9、17、24、4、15、21、6、7、10、2以及14,主成分二則包含Cp G19及22,主成分三只包含Cp G22。女性睡眠質(zhì)量差組與睡眠質(zhì)量?jī)?yōu)組主成分分別為6個(gè)及7個(gè),每個(gè)主成分包含的Cp G位點(diǎn)數(shù)量為3至4個(gè)。男女睡眠質(zhì)量差組m RNA相對(duì)表達(dá)量及TM蛋白水平均高于睡眠質(zhì)量?jī)?yōu)組。結(jié)論:TM基因啟動(dòng)子區(qū)DNA甲基化水平總體上與代謝指標(biāo)及中淋比無(wú)關(guān)。高血壓人群不同睡眠質(zhì)量組間的TM基因啟動(dòng)子區(qū)Cp G位點(diǎn)DNA甲基化水平,甲基化修飾分布范圍及各位點(diǎn)DNA甲基化關(guān)聯(lián)特點(diǎn)的明顯差異可能與TM蛋白的基因表達(dá)調(diào)控明確相關(guān)。
[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.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2017
【分類(lèi)號(hào)】:R544.1


本文編號(hào):1944262

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