血压波动及血管紧张素原基因多态性与皮层下动脉硬化性脑病相关研究

发布时间：2019-07-09 20:21

【摘要】：研究背景：皮层下动脉硬化性脑病（Binswange’rs Disease, BD),具有起病隐袭、进行性加重的特点，是皮质下血管性痴呆的重要组成部分之一。典型者临床表现为高血压、卒中发作史、执行功能（包括抽象思维、概念形成和转换、信息处理速度等[1])障碍为主的慢性进行性痴呆，而局灶性体征主要表现为步态不稳、假性球麻痹、尿失禁等，且常伴有情感和行为异常。影像学的发展使其发现率日益增加，也因其严重的社会后果及逐渐增加的临床发现率引起人们的关注。目前的研究多集中在危险因素等方面，高血压[2]被认为是其最重要的独立危险因素。血压波动性是指24小时内血压水平的自发性变化。无创性动态血压监测技术的应用，使得血压波动性异常与靶器官损伤的关系倍受关注。有研究[3]证实，血压波动在靶器官损伤中的重要性不亚于血压水平[[，且是心4]、脑5]血管疾病的重要危险因素。肾素-血管紧张素系统（Renin-angiotensin system, RAS)在高血压发病、血压调控及血压昼夜节律形态变化中起到重要作用，而作为肾素作用底物的血管紧张素原（Angiotensinogen,AGT)，其地位尤为重要。AGT合成的调节主要是基因转录水平的调节，故AGT基因结构可能与原发高血压或者其他以血压水平升高为主要临床表现的疾病存在相关性。AGT基因错义突变M235T在人群中的出现率比较高，且经多项研究证实其与原发性高血压病[6]及血管性痴呆[7](vasulardementia,vd)存在相关性，故提出假设：1、血压波动或血压昼夜节律形态异常与bd相关。2、agtm235t基因多态性与bd存在相关性。3、agtm235t可通过影响血压波动性或血压昼夜节律，从而与bd的发生或者发展相关。目的：1、探讨血压波动性、血压昼夜节律形态与bd的关系；2、研究agtm235t基因多态性与bd的关系。3、探讨bd患者血压昼夜形态与agtm235t基因多态性的关系。方法：临床入组皮层下动脉硬化性脑病患者122例为皮层下动脉硬化性脑病组(bd组），单纯原发性高血压患者108例为单纯原发性高血压组（eh组），正常健康查体者71例为正常对照组，分别对所有的入组者进行甘油三酯(tg)、胆固醇(cho)、低密度脂蛋白（ldl)、尿素氮(bun)、肌酐(cr)、谷丙转氨酶ult)、谷草转氨酶(ast)、空腹血糖(fbg)水平检测，以及agtm235t基因型检测；将mm基因型与mt基因型归为同组；对bd组及eh组的所有患者进行24小时动态血压监测;对agtm235t基因型及m/t等位基因在三组间的分布频率及bd组和eh组间血压波动、昼夜节律形态进行统计分析；同时对bd组血压昼夜节律形态与agtm235t基因分布频率相关性进行分析。结果：1、三组间一般资料的比较bd组、eh病组血压水平差异无统计学意义(尸0.05);bd组、eh病组及正常对照组间tg、cho、ldl、ast、alt、bun、cr、fbg水平差异亦无统计学意义（厂0.05)。2、hardy-weinberg遗传平衡检验结果bd组、eh组、正常对照组三组间的agtm235t基因型分布符合hardy-weinberg分布，实际检出基因型在各组内的分布频率与预期基本一致。3、三组间agtm235t基因多态性比较：3-1、mm+mt基因型在bd组及正常对照组间的分布频率差异无统计学意义（尸〉0.05)。 3-2、MM+MT基因型在BD组的分布频率明显高于EH组（尸〈0.01)。 3-3、TT基因型及T等位基因在EH组的分布频率明显高于正常对照组（P0.01)。 4、BD组及EH组间血压波动性、血压昼夜节律形态比较： 4-1、BD组夜间舒张压及收缩压波动、24小时舒张压波动水平明显高于EH组(尸0.05)。 4-2、反杓型血压昼夜节律形态在BD组的分布高于EH组（P0.01)。 5、BD组患者AGTM235T基因多态性与血压昼夜节律形态间相关性比较：BD患者中AGTM235T基因型表现为MM+MT基因型者，其血压昼夜节律形态更多的表现为反杓型。结论： 1、AGTM235T基因MM或MT基因型与BD相关，AGT M235T基因TT基因型及T等位基因与原发性高血压相关，而AGT M235T基因型表现为MT或MM型的EH患者可能更易患BD。 2、BD患者夜间血压及24小时舒张压波动明显，，且夜间血压异常升高;AGTM235T基因的MM+MT基因型或M等位基因可能通过影响血压昼夜形态，从而参与了BD的发生和发展。本实验有助于在原发性高血压患者中发现BD的高危人群，从而对高危人群进行早期预防，对已发生BD的患者注意其夜间血压水平及血压波动性的控制，最终降低VD的发生率或者延缓BD的进展。
[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.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R544.1;R749.1

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