积极降压对脑小血管病防治策略的影响

2017年,美国心脏病学会和美国心脏协会提出将高血压诊断标准降为130/80 mm Hg (1 mm Hg=0. 133 kPa),这与其他指南有所不同。降压治疗的核心目标在于靶器官的保护,近年来降压治疗与脑小血管病预防的相关问题日益受到临床重视。目前研究结果表明,降压治疗对腔隙性卒中患者的二级预防以及白质病变进展的预防可能有一定积极意义,但确切的降压目标值并未确定。血压与临床结局可能呈现J型关系,血压过低或过高可能均有害,而取得最大获益的降压目标有待进一步探索。     

原发性高血压病靶器官损害的预测仿真研究

研究原发性高血压病靶器官损害准确预测问题,由于原发性高血压病靶器官损害的影响因子之间存在着高度冗余和非线性,导致传统方法预测准确率低,为提高预测精度,构建了一种改进的基因表达式编程算法的原发性高血压病靶器官损害预测模型,首先设计了适合靶器官损害预测的适应度函数,然后为克服早熟现象提出了以平均适应度形式自适应的改变重组算子概率和变异算子概率,通过数据训练得到靶器官损害的2年预测模型。采用对山东中医药大学第二附属医院原发性高血压病历史数据进行验证性仿真,结果表明,方法的预测精度更高,在原发性高血压病靶器官损害的预测中有着广泛的应用前景。     

ZigBee在动态血压监测中的应用研究

我国已成为世界上高血压危害最严重的国家之一,在全国范围大力开展高血压病的防治,积极治疗高血压病患者,已经刻不容缓.通过研究ZigBee技术,提出了以ZigBee无线传感器网络为核心,以以太网为骨干网,采用CC2430芯片为血压传感器控制核心的动态血压测量方案,系统测量的收缩压、舒张压误差范围均小于5mmHg.试验证明,系统能够实时监测患者的血压变化,工作稳定可靠,具有较高的实用性和市场价值.     

高血压形成与发展的血流动力学分析

根据作者提出的血流动力学参数计算公式,研究了不同年令和不同血压下血流动力学参数的变化从中得出外周阻力的增高是高血压最主要的危险因素。并经理论分析和临床实测证实了这个结论。     

高血压患者脉博信号的采集与频谱分析

根据人体脉博信号的特点,提出了一种对脉搏声信号进行检测和数据采集的方法。讨论了脉搏声信号采集和处理过程中各参数之间的关系及应选取的指标,介绍了脉搏信号的一种频域分析方法——功率谱分析,获得了两种脉搏信号的功率谱图。取检测对象１０８例,其中通过对６５例高血压患者、４３例健康人作为对照组的脉象信号的功率谱计算,发现高血压患者脉搏功率谱高频部分的能量分布较健康人发生了明显的变化,并从人体生理病理学的角度分析了变化的可能原因。得出了对高血压疾病的临床诊断有参考价值的结论     

A Novel Mouse Model of TGFβ2-Induced Ocular Hypertension Using Lentiviral Gene Delivery

Glaucoma is a multifactorial disease leading to irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form and is associated with the elevation of intraocular pressure (IOP). Reduced aqueous humor (AH) outflow due to trabecular meshwork (TM) dysfunction is responsible for IOP elevation in POAG. Extracellular matrix (ECM) accumulation, actin cytoskeletal reorganization, and stiffening of the TM are associated with increased outflow resistance. Transforming growth factor (TGF) β2, a profibrotic cytokine, is known to play an important role in the development of ocular hypertension (OHT) in POAG. An appropriate mouse model is critical in understanding the underlying molecular mechanism of TGFβ2-induced OHT. To achieve this, TM can be targeted with recombinant viral vectors to express a gene of interest. Lentiviruses (LV) are known for their tropism towards TM with stable transgene expression and low immunogenicity. We, therefore, developed a novel mouse model of IOP elevation using LV gene transfer of active human TGFβ2 in the TM. We developed an LV vector-encoding active hTGFβ2^C226,228S under the control of a cytomegalovirus (CMV) promoter. Adult C57BL/6J mice were injected intravitreally with LV expressing null or hTGFβ2^C226,228S. We observed a significant increase in IOP 3 weeks post-injection compared to control eyes with an average delta change of 3.3 mmHg. IOP stayed elevated up to 7 weeks post-injection, which correlated with a significant drop in the AH outflow facility (40.36%). Increased expression of active TGFβ2 was observed in both AH and anterior segment samples of injected mice. The morphological assessment of the mouse TM region via hematoxylin and eosin (H&E) staining and direct ophthalmoscopy examination revealed no visible signs of inflammation or other ocular abnormalities in the injected eyes. Furthermore, transduction of primary human TM cells with LV_hTGFβ2^C226,228S exhibited alterations in actin cytoskeleton structures, including the formation of F-actin stress fibers and crossed-linked actin networks (CLANs), which are signature arrangements of actin cytoskeleton observed in the stiffer fibrotic-like TM. Our study demonstrated a mouse model of sustained IOP elevation via lentiviral gene delivery of active hTGFβ2^C226,228S that induces TM dysfunction and outflow resistance.     

Intermittent Hypoxia Increased the Expression of DBH and PNMT in Neuroblastoma Cells via MicroRNA-375-Mediated Mechanism

Sleep apnea syndrome (SAS), characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia (IH)), is a risk factor for hypertension and insulin resistance. We report a correlation between IH and insulin resistance/diabetes. However, the reason why hypertension is induced by IH is elusive. Here, we investigated the effect of IH on the expression of catecholamine-metabolizing enzymes using an in vitro IH system. Human and mouse neuroblastoma cells (NB-1 and Neuro-2a) were exposed to IH or normoxia for 24 h. Real-time RT-PCR revealed that IH significantly increased the mRNA levels of dopamine β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in both NB-1 and Neuro-2a. Western blot showed that the expression of DBH and PNMT in the NB-1 cells was significantly increased by IH. Reporter assays revealed that promoter activities of DBH and PNMT were not increased by IH. The miR-375 level of IH-treated cells was significantly decreased relative to that of normoxia-treated cells. The IH-induced up-regulation of DBH and PNMT was abolished by the introduction of the miR-375 mimic, but not by the control RNA. These results indicate that IH stress increases levels of DBH and PNMT via the inhibition of miR-375-mediated mRNA degradation, potentially playing a role in the emergence of hypertension in SAS patients.     

Primary Aldosteronism and Resistant Hypertension: A Pathophysiological Insight

Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are “high-risk phenotypes”, associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of “non-classical” effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.     

基于交感神经系统的高血压非药物治疗研究现状和进展

高血压病是一种危害人类健康的严重疾病,尽管高血压的临床治疗已经取得较好疗效,但仍存在不少药物耐受性等不同类型的顽固性高血压,而且高血压的并发症如心力衰竭、脑卒中等发病率仍居高不下,因此,非药物治疗策略的深入研发与应用已成为高血压治疗的一个重要方面。交感神经系统在高血压发生发展中起着关键性作用,目前大多数高血压防治的非药物治疗技术主要通过靶向调节机体交感神经功能来实现,这些技术主要包括深部脑刺激、肾动脉神经射频消融术、中央髂动静脉吻合术、压力反射激活疗法、血管内压力反射放大疗法、颈动脉体切除术等。本综述重点对上述基于交感神经系统的非药物治疗方法的应用现状和相关优缺点进行回顾总结,为高血压的有效治疗提供新思路和多重选择。     

老年高血压患者脉压指数与尿微量白蛋白/尿肌酐、血清视黄醇结合蛋白的关系

目的 探讨老年原发性高血压（EH）患者脉压指数（PPI）与尿微量白蛋白/尿肌酐（尿mAlb/尿Cr）、血清视黄醇结合蛋白（RBP）的关系.方法 选取血肌酐（Cr）正常的老年EH患者50例（EH组,根据PPI分为PPI＆lt;0.5组及≥0.5组）及健康体检的老年人20例（对照组）.比较各组尿mAlb/尿Cr比值、血清RBP的变化及与PPI的相关性.结果 尿mAlb/尿Cr比值、血清RBP值比较：EH组高于对照组,PPI≥0.5组高于PPI＆lt;0.5组（均P＆lt;0.05）;尿mAlb/尿Cr比值联合血清RBP值阳性率比较：PPI≥0.5组高于PPI＆lt;0.5组（63.64%比28.57%,P＆lt;0.05）;PPI与尿mAlb/尿Cr比值、血清RBP值呈正相关（r=0.425,P=0.019;r=0.401,P=0.032）.结论 老年EH患者PPI与尿mAlb/尿Cr、血清RBP密切相关,联合检测可作为老年EH患者早期肾功能损害的一个评估指标.