血壓波動及血管緊張素原基因多態(tài)性與皮層下動脈硬化性腦病相關研究
發(fā)布時間：2019-07-09 20:21
【摘要】：研究背景：皮層下動脈硬化性腦病（Binswange’rs Disease, BD),具有起病隱襲、進行性加重的特點，是皮質(zhì)下血管性癡呆的重要組成部分之一。典型者臨床表現(xiàn)為高血壓、卒中發(fā)作史、執(zhí)行功能（包括抽象思維、概念形成和轉(zhuǎn)換、信息處理速度等[1])障礙為主的慢性進行性癡呆，而局灶性體征主要表現(xiàn)為步態(tài)不穩(wěn)、假性球麻痹、尿失禁等，且常伴有情感和行為異常。影像學的發(fā)展使其發(fā)現(xiàn)率日益增加，也因其嚴重的社會后果及逐漸增加的臨床發(fā)現(xiàn)率引起人們的關注。目前的研究多集中在危險因素等方面，高血壓[2]被認為是其最重要的獨立危險因素。 血壓波動性是指24小時內(nèi)血壓水平的自發(fā)性變化。無創(chuàng)性動態(tài)血壓監(jiān)測技術的應用，使得血壓波動性異常與靶器官損傷的關系倍受關注。有研究[3]證實，血壓波動在靶器官損傷中的重要性不亞于血壓水平[[，且是心4]、腦5]血管疾病的重要危險因素。 腎素-血管緊張素系統(tǒng)（Renin-angiotensin system, RAS)在高血壓發(fā)病、血壓調(diào)控及血壓晝夜節(jié)律形態(tài)變化中起到重要作用，而作為腎素作用底物的血管緊張素原（Angiotensinogen,AGT)，其地位尤為重要。AGT合成的調(diào)節(jié)主要是基因轉(zhuǎn)錄水平的調(diào)節(jié)，故AGT基因結構可能與原發(fā)高血壓或者其他以血壓水平升高為主要臨床表現(xiàn)的疾病存在相關性。AGT基因錯義突變M235T在人群中的出現(xiàn)率比較高，且經(jīng)多項研究證實其與原發(fā)性高血壓病[6]及血管性癡呆[7](vasulardementia,vd)存在相關性，故提出假設：1、血壓波動或血壓晝夜節(jié)律形態(tài)異常與bd相關。2、agtm235t基因多態(tài)性與bd存在相關性。3、agtm235t可通過影響血壓波動性或血壓晝夜節(jié)律，從而與bd的發(fā)生或者發(fā)展相關。目的：1、探討血壓波動性、血壓晝夜節(jié)律形態(tài)與bd的關系；2、研究agtm235t基因多態(tài)性與bd的關系。3、探討bd患者血壓晝夜形態(tài)與agtm235t基因多態(tài)性的關系。方法：臨床入組皮層下動脈硬化性腦病患者122例為皮層下動脈硬化性腦病組(bd組），單純原發(fā)性高血壓患者108例為單純原發(fā)性高血壓組（eh組），正常健康查體者71例為正常對照組，分別對所有的入組者進行甘油三酯(tg)、膽固醇(cho)、低密度脂蛋白（ldl)、尿素氮(bun)、肌酐(cr)、谷丙轉(zhuǎn)氨酶ult)、谷草轉(zhuǎn)氨酶(ast)、空腹血糖(fbg)水平檢測，以及agtm235t基因型檢測；將mm基因型與mt基因型歸為同組；對bd組及eh組的所有患者進行24小時動態(tài)血壓監(jiān)測;對agtm235t基因型及m/t等位基因在三組間的分布頻率及bd組和eh組間血壓波動、晝夜節(jié)律形態(tài)進行統(tǒng)計分析；同時對bd組血壓晝夜節(jié)律形態(tài)與agtm235t基因分布頻率相關性進行分析。結果：1、三組間一般資料的比較bd組、eh病組血壓水平差異無統(tǒng)計學意義(尸0.05);bd組、eh病組及正常對照組間tg、cho、ldl、ast、alt、bun、cr、fbg水平差異亦無統(tǒng)計學意義（廠0.05)。2、hardy-weinberg遺傳平衡檢驗結果bd組、eh組、正常對照組三組間的agtm235t基因型分布符合hardy-weinberg分布，實際檢出基因型在各組內(nèi)的分布頻率與預期基本一致。3、三組間agtm235t基因多態(tài)性比較：3-1、mm+mt基因型在bd組及正常對照組間的分布頻率差異無統(tǒng)計學意義（尸〉0.05)。 3-2、MM+MT基因型在BD組的分布頻率明顯高于EH組（尸〈0.01)。 3-3、TT基因型及T等位基因在EH組的分布頻率明顯高于正常對照組（P0.01)。 4、BD組及EH組間血壓波動性、血壓晝夜節(jié)律形態(tài)比較： 4-1、BD組夜間舒張壓及收縮壓波動、24小時舒張壓波動水平明顯高于EH組(尸0.05)。 4-2、反杓型血壓晝夜節(jié)律形態(tài)在BD組的分布高于EH組（P0.01)。 5、BD組患者AGTM235T基因多態(tài)性與血壓晝夜節(jié)律形態(tài)間相關性比較：BD患者中AGTM235T基因型表現(xiàn)為MM+MT基因型者，其血壓晝夜節(jié)律形態(tài)更多的表現(xiàn)為反杓型。 結論： 1、AGTM235T基因MM或MT基因型與BD相關，AGT M235T基因TT基因型及T等位基因與原發(fā)性高血壓相關，而AGT M235T基因型表現(xiàn)為MT或MM型的EH患者可能更易患BD。 2、BD患者夜間血壓及24小時舒張壓波動明顯，，且夜間血壓異常升高;AGTM235T基因的MM+MT基因型或M等位基因可能通過影響血壓晝夜形態(tài)，從而參與了BD的發(fā)生和發(fā)展。 本實驗有助于在原發(fā)性高血壓患者中發(fā)現(xiàn)BD的高危人群，從而對高危人群進行早期預防，對已發(fā)生BD的患者注意其夜間血壓水平及血壓波動性的控制，最終降低VD的發(fā)生率或者延緩BD的進展。
[Abstract]:Background: The characteristic of the subcortical arteriosclerotic encephalopathy (BD), which is characterized by the onset of disease and the progressive addition, is one of the important components of the vascular dementia in the cortex. The typical clinical manifestations are hypertension, stroke history, executive function (including abstract thinking, concept formation and conversion, information processing speed, etc.[1]). And often accompanied by an abnormality of emotion and behavior. The development of image has increased its discovery rate, and it is also concerned about the serious social consequences and the increasing rate of clinical findings. High blood pressure[2] is considered to be the most important independent risk factor in the current study on risk factors. The fluctuation of blood pressure refers to the spontaneous change of blood pressure level within 24 hours The application of non-invasive dynamic blood pressure monitoring technology makes the relationship between abnormal blood pressure fluctuation and target organ damage. Note: Studies[3] confirm that the importance of blood pressure fluctuations in target organ damage is no less important than the blood pressure level[[, and is the heart 4], the brain 5] the important risk of vascular disease, The renin-angiotensin system (RAS) plays an important role in the pathogenesis of hypertension, the regulation of blood pressure and the changes of the circadian rhythm of blood pressure. It is important that the regulation of AGT synthesis is mainly the regulation of the gene transcription level, so the AGT gene structure may be related to the primary hypertension or other diseases with the main clinical manifestation elevated as the blood pressure level The correlation was found to be related to the occurrence rate of the AAGT gene missense mutation M235T in the population, and the relationship between the primary hypertension[6] and the vascular dementia[7] (vasulardementia, vd) was confirmed by a number of studies. the relationship between the polymorphism of the agtm235t gene and the bd.3, agtm235t may be related to the occurrence or generation of the bd by affecting the blood pressure fluctuation or the blood pressure circadian rhythm, Objective:1. To study the relationship between the blood pressure fluctuation, the circadian rhythm of blood pressure and the bd, and to study the relationship between the polymorphism of the agtm235t gene and the bd. Methods:122 patients with arteriosclerotic encephalopathy (n = 122) were in the subcortical arteriosclerotic encephalopathy group (group bd). In the control group, the triglyceride (tg), the cholesterol (cho), the low-density lipoprotein (ldl), the urea nitrogen (bun), the muscle pressure (cr), the glutamic-pyruvic transaminase result), the aspartate aminotransferase (ast), the fasting blood glucose (fbg) level detection, and the agtm235t gene were performed on all the enrolled subjects, respectively. type detection; grouping the mm genotype and the mt genotype into the same group; performing 24-hour ambulatory blood pressure monitoring on all patients in the bd-group and the eh group; comparing the distribution frequency of the agtm235t genotype and the m/ t allele between the three groups and the blood pressure fluctuation and the circadian rhythm of the bd-and h-groups; the relationship between the circadian rhythm of the blood pressure of the bd and the distribution of the agtm235t gene in the bd-group The results were as follows:1. There was no significant difference in the level of blood pressure between the three groups (P0.05). There was no significant difference in the levels of tg, cho, ldl, ast, alt, bun, cr, fbg in the bd group, the h disease group and the normal control group (factory 0.05). ).2. The distribution of agtm235t between the three groups of the three groups was consistent with the expected. The distribution frequency of the 3-1, mm + mt genotypes in the bd group and the normal control group was not statistically significant (body> 0. 05). The distribution frequency of the 3-2, MM + MT genotypes in the BD group was significantly higher than that of the EH group (body < The distribution frequency of 3-3, TT genotype and T allele in EH group was significantly higher than that of normal control group. (P0.01). Blood pressure fluctuation and blood in the groups of 4, BD and EH groups Comparison of the circadian rhythm of the circadian rhythm:4-1, the diastolic blood pressure and the systolic pressure in the BD group, and the fluctuation of the diastolic blood pressure in the 24-hour period was significantly higher. In the EH group (body 0.05).4-2, the circadian rhythm of the blood pressure of the reverse-type blood pressure was in the group of the BD group. The relationship between the polymorphism of AGTM235T gene and the circadian rhythm of blood pressure in patients with BD was higher than that in EH group (P0.01). day and night Conclusion:1, AGTM235T gene MM or MT genotype is associated with BD, AGT M235T gene TT genotype and T allele are related to essential hypertension, and AGT M235T genotype For EH patients of type MT or MM, it may be more likely to develop BD.2. The blood pressure in the patients with BD and the diastolic blood pressure at night are obvious, and the abnormal increase of blood pressure at night; the MM + MT genotype or the M allele of the AGTM235T gene may pass through the shadow In response to the day-and-night morphology of the blood pressure, the occurrence and development of BD were involved. This experiment was helpful to the detection of high-risk population of BD in patients with essential hypertension, so as to prevent the high-risk population. The blood pressure level and blood pressure fluctuation of patients with BD were noted.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R544.1;R749.1
本文編號：2512420
[Abstract]:Background: The characteristic of the subcortical arteriosclerotic encephalopathy (BD), which is characterized by the onset of disease and the progressive addition, is one of the important components of the vascular dementia in the cortex. The typical clinical manifestations are hypertension, stroke history, executive function (including abstract thinking, concept formation and conversion, information processing speed, etc.[1]). And often accompanied by an abnormality of emotion and behavior. The development of image has increased its discovery rate, and it is also concerned about the serious social consequences and the increasing rate of clinical findings. High blood pressure[2] is considered to be the most important independent risk factor in the current study on risk factors. The fluctuation of blood pressure refers to the spontaneous change of blood pressure level within 24 hours The application of non-invasive dynamic blood pressure monitoring technology makes the relationship between abnormal blood pressure fluctuation and target organ damage. Note: Studies[3] confirm that the importance of blood pressure fluctuations in target organ damage is no less important than the blood pressure level[[, and is the heart 4], the brain 5] the important risk of vascular disease, The renin-angiotensin system (RAS) plays an important role in the pathogenesis of hypertension, the regulation of blood pressure and the changes of the circadian rhythm of blood pressure. It is important that the regulation of AGT synthesis is mainly the regulation of the gene transcription level, so the AGT gene structure may be related to the primary hypertension or other diseases with the main clinical manifestation elevated as the blood pressure level The correlation was found to be related to the occurrence rate of the AAGT gene missense mutation M235T in the population, and the relationship between the primary hypertension[6] and the vascular dementia[7] (vasulardementia, vd) was confirmed by a number of studies. the relationship between the polymorphism of the agtm235t gene and the bd.3, agtm235t may be related to the occurrence or generation of the bd by affecting the blood pressure fluctuation or the blood pressure circadian rhythm, Objective:1. To study the relationship between the blood pressure fluctuation, the circadian rhythm of blood pressure and the bd, and to study the relationship between the polymorphism of the agtm235t gene and the bd. Methods:122 patients with arteriosclerotic encephalopathy (n = 122) were in the subcortical arteriosclerotic encephalopathy group (group bd). In the control group, the triglyceride (tg), the cholesterol (cho), the low-density lipoprotein (ldl), the urea nitrogen (bun), the muscle pressure (cr), the glutamic-pyruvic transaminase result), the aspartate aminotransferase (ast), the fasting blood glucose (fbg) level detection, and the agtm235t gene were performed on all the enrolled subjects, respectively. type detection; grouping the mm genotype and the mt genotype into the same group; performing 24-hour ambulatory blood pressure monitoring on all patients in the bd-group and the eh group; comparing the distribution frequency of the agtm235t genotype and the m/ t allele between the three groups and the blood pressure fluctuation and the circadian rhythm of the bd-and h-groups; the relationship between the circadian rhythm of the blood pressure of the bd and the distribution of the agtm235t gene in the bd-group The results were as follows:1. There was no significant difference in the level of blood pressure between the three groups (P0.05). There was no significant difference in the levels of tg, cho, ldl, ast, alt, bun, cr, fbg in the bd group, the h disease group and the normal control group (factory 0.05). ).2. The distribution of agtm235t between the three groups of the three groups was consistent with the expected. The distribution frequency of the 3-1, mm + mt genotypes in the bd group and the normal control group was not statistically significant (body> 0. 05). The distribution frequency of the 3-2, MM + MT genotypes in the BD group was significantly higher than that of the EH group (body < The distribution frequency of 3-3, TT genotype and T allele in EH group was significantly higher than that of normal control group. (P0.01). Blood pressure fluctuation and blood in the groups of 4, BD and EH groups Comparison of the circadian rhythm of the circadian rhythm:4-1, the diastolic blood pressure and the systolic pressure in the BD group, and the fluctuation of the diastolic blood pressure in the 24-hour period was significantly higher. In the EH group (body 0.05).4-2, the circadian rhythm of the blood pressure of the reverse-type blood pressure was in the group of the BD group. The relationship between the polymorphism of AGTM235T gene and the circadian rhythm of blood pressure in patients with BD was higher than that in EH group (P0.01). day and night Conclusion:1, AGTM235T gene MM or MT genotype is associated with BD, AGT M235T gene TT genotype and T allele are related to essential hypertension, and AGT M235T genotype For EH patients of type MT or MM, it may be more likely to develop BD.2. The blood pressure in the patients with BD and the diastolic blood pressure at night are obvious, and the abnormal increase of blood pressure at night; the MM + MT genotype or the M allele of the AGTM235T gene may pass through the shadow In response to the day-and-night morphology of the blood pressure, the occurrence and development of BD were involved. This experiment was helpful to the detection of high-risk population of BD in patients with essential hypertension, so as to prevent the high-risk population. The blood pressure level and blood pressure fluctuation of patients with BD were noted.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R544.1;R749.1
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