大规模人群中原发性高血压发病机制中盐敏感性和交感神经调节的遗传作用（研究方案及预试验）

目的　探讨在中国汉族人群中 ,盐敏感及交感神经调节的影响在原发性高血压发病机制中的作用。方法学　在选定的现场调查中心对该地区所登记的家庭进行随机抽样 ,同时在指定的高血压门诊筛选病人 ,最终共入选 2 0 0个家庭、约 10 0 0位受试者。采用连锁分析方法对入选家庭中年龄为 18～ 5 9岁的核心成员肾素系统的遗传变异与血压及高血压之间的关系进行研究。采用严格标准化的流行病学调查方法、严格的质量控制来确定血压与其他特征相结合的综合表型。常规血压为 2次独立家访测量的血压 (共 10个读数 )的平均值。确定综合表型的方法包括 2 4小时动态血压监测 ,作为心血管系统自主调节指数的心率变异性能谱分析及作为钠敏感性的内源性锂清除率测定。问卷将调查个人及家庭的医疗史及重要的生活方式。除血常规检查 ,还将测定血生化及血浆肾素活性、血管紧张素原浓度及血管紧张素转换酶的活性及 2 4小时尿电解质排泄量。预期结果　在中国 ,高血压的标化患病率为 11.2 6 % [2 ] ,其主要并发症为脑卒中 ,而后者是致残的主要危险。本研究将促进我国心血管疾病遗传学的研究 ,将有助于高血压及其并发症的预防及治疗 ,对我国公共卫生事业具有重要意义。预试验结果　共调查 4 8例 (男 2 0 ,女 2 8) ,平均年龄 38.6±     

福辛普利对原发性高血压患者降压作用和对内皮功能的影响

目的评价福辛普利对轻、中度原发性高血压患者的降压疗效,以及对原发性高血压患者内皮功能和肾素-血管紧张素系统(RAS)影响的机制.方法60例原发性高血压患者,随机分为福辛普利组30例和吲哒帕胺组30例.观察治疗前与治疗后6周,诊所血压(CBP)、血浆一氧化氮、内皮素、肾素活性、血管紧张素Ⅱ和醛固酮浓度变化,并对CBP和RAS、血压水平与内皮功能之间的相关性进行分析.结果治疗后2组血压水平显著下降,福辛普利组收缩压从160士14mmHg降至149±13mmHg,舒张压从96±7mmHg降至84±6mmHg,吲哒帕胺组收缩压从161±16mmHg降至154±14mmHg,舒张压从94±6mmHg降至85±7mmHg,差异有极显著性(P均＜0.001).福辛普利组血浆一氧化氮升高,肾素活性上升,内皮素下降,血管紧张素Ⅱ下降,醛固酮下降,差异有极显著性(P均＜0.001),吲哒帕胺组上述参数未见明显变化(P均＞0.05).结论福辛普利对于轻、中度原发性高血压患者疗效显著,福辛普利降压同时能改善动脉内皮功能,降低RAS活性.     

胰腺肾素-血管紧张素系统与临床疾病的相关性

传统肾素.血管紧张素系统(renin-angiotensin system,RAS)被定义为循环相关系统,由血管紧张素原、肾素及血管紧张素转换酶、血管紧张素Ⅱ及其受体等组成,主要参与调节血压、水及电解质平衡.     

银丹心脑通软胶囊对高血压病人血压变异性的影响

目的探讨高血压病人使用银丹心脑通软胶囊对血压变异性的影响。方法抽取2013年9月—2015年1月在我院治疗基础人98例高血压病人,根据治疗方法分为对照组和观察组,每组49例,对照组采用常规治疗,观察组在常规治疗的同时配合银丹心脑通软胶囊治疗。两组均在治疗前后检测一氧化氮、血浆肾素、内皮素、血管紧张素Ⅱ和血压变异性水平。结果观察组治疗后血压变异性明显低于对照组(收缩压:0.27 mmHg±0.03 mmHg vs 0.39 mmHg±0.01 mmHg;舒张压:0.25 mmHg±0.02 mmHg vs0.34 mmHg±0.03 mmHg,P0.05);两组治疗后一氧化氮水平明显升高,血浆肾素、内皮素和血管紧张素水平明显降低(P0.05)。结论高血压病人在使用常规治疗的同时配合银丹心脑通软胶囊,有利于降低血压,减小血压变异性。     

肾素—血管紧张素系统与身体功能

过去20年来,对肾素—血管紧张素系统(RAS)的生化学知识,以及它在调节体液电解质平衡、血压和其它生理功能的认识,都取得了显著的进展。 RAS的生物化学 一、肾素:肾素是在肾近球旁器(JG)细胞合成的一种酸性蛋白酶,能裂解血管紧张素原释出血管紧张素Ⅰ(AT-Ⅰ)。有证据表明,肾素合成中有一大分子量的无活性前体;无活性的肾素在体外可通过各种酸化作用或冷处理而转变为活性的肾素,但在体内是如何被激活的则尚不清楚。肾素合成和     

肝控制血管紧张素原的合成与分泌

肾素—血管紧张素系统(RAS)在调节血压与水盐平衡中起重要作用,与肾性高血压、甚至特发性高血压的发病机制有关。 催化血管紧张素合成的酶体系,是由循环中血管紧张素原(ATG)与肾素反应而     

REN基因变异与降压药物作用下血压及相关临床表型变化的关系

目的 探讨新疆哈萨克族原发性高血压患者肾素基因rs1464816基因型与研究对象服用降压药物前后血压及相关临床表型水平变化的关系.方法 随机选择新疆18～69岁1218名哈萨克族农牧民进行高血压相关危险因素横断面调查,筛选出首次诊断为高血压并未接受过降压治疗和无其他并发症共计400人作为研究对象.研究对象随机分为两组,分别服用血管紧张素转换酶抑制剂卡托普利和β受体阻滞剂阿替洛尔.两组均服药3周,应用聚合酶链式反应-连接酶检测反应(PCR-LDR)检测研究对象肾素基因rs1464816基因型,分析其与服用降压药物前后研究对象血压及相关临床表型(包括血浆肾素、血管紧张素Ⅱ及醛固酮)水平变化的关系.结果 肾素基因rs1464816经Hardy-Weinberg遗传平衡检验不平衡;未发现肾素基因rs1464816基因型与收缩压、舒张压、血浆肾素、血管紧张素Ⅱ和醛固酮用药前后水平变化有关.结论 新疆哈萨克族原发性高血压患者肾素基因rs1464816基因型与收缩压、舒张压、血浆肾素、血管紧张素Ⅱ和醛固酮用药前后变化无关.     

整夜完全睡眠剥夺对某部队军人动态血压的影响

目的探讨急性睡眠剥夺对驻军某部队军人动态血压各项指标的影响及可能的发生机制。方法选择驻军某部队60名健康军人进行横断面研究,采用24 h整夜完全睡眠剥夺方法。在睡眠剥夺过程中应用动态血压记录仪监测血压等各项指标。睡眠剥夺后检测儿茶酚胺(多巴胺、肾上腺素和去甲肾上腺素)、肾素、血管紧张素和醛固酮水平。恢复1周后再次检测血儿茶酚胺水平作为对照。结果睡眠剥夺后:(1)夜间血压负荷增高,夜间收缩压负荷为55.3%±37.0%,夜间舒张压负荷为26.5%±28.8%;(2)血儿茶酚胺水平升高,与恢复期比较差异有统计学意义[多巴胺(8.76±2.63)μg/L比(7.44±2.54)μg/L,肾上腺素(31.91±11.79)μg/L比(25.58±8.51)μg/L,去甲肾上腺素(2.12±1.03)μg/L比(1.27±0.47)μg/L]。肾上腺素水平与平均心率呈正相关(r=0.446,P<0.05)。肾素、血管紧张素和醛固酮水平升高[肾素(3.33±2.00)nmol.L-1.h-1,血管紧张素Ⅱ(67.98±27.46)ng/L,醛固酮(495.58±70.04)pmol/L]。结论急性整夜完全睡眠剥夺可导致健康成年男性夜间血压负荷增高,昼夜节律消失,是高血压发生的危险因素,可能会增加心血管事件的风险。睡眠剥夺后血儿茶酚胺、肾素、血管紧张素和醛固酮水平升高,提示儿茶酚胺与肾素-血管紧张素-醛固酮系统可能共同参与动态血压的调节。     

氯沙坦及氯沙坦与双氢克尿噻合剂对原发性高血压患者肾素活性影响的比较

目的比较血管紧张素Ⅱ受体拮抗剂氯沙坦及氯沙坦与双氢克尿噻合剂对原发性高血压患者的降压疗效和肾素活性水平的影响。 方法坐位舒张压95～115mmHg(1mmHg=0.133kPa)的76例原发性高血压患者,经1周药物洗脱期,2周安慰剂期后,随机服用氯沙坦50mg(氯沙坦组,n=37),每日1次或氯沙坦50mg与双氢克尿噻12.5mg合剂(氯沙坦+双氢克尿噻合剂组,n=39),每日1次。4周末坐位舒张压≥90mmHg者,剂量分别加倍,继续服用4周。于安慰剂期末及服药8周末测量诊室坐位血压和测定立位血浆肾素活性水平。 结果服药8周末平均坐位舒张压氯沙坦组(n=35)下降10.1±9.1mmHg;氯沙坦+双氢克尿噻合剂组(n=33)下降14.6±7.5mmHg(组间比较P＜0.05);同时服用末次药24小时后氯沙坦组的平均血浆肾素活性从1.6ng/(ml*h)增加至5.4ng/(ml     

肾素抑制剂研究新进展

近年来大量研究证实,抑制肾素血管紧张素系统(renin angiotensin system, RAS)对治疗心血管疾病、肾脏疾病及糖尿病并发症等具有良好的效果.众所周知,经典的RAS通过以下途径激活:血管紧张素原在肾素作用下生成无活性的十肽:血管紧张素Ⅰ,后者经血管紧张素转换酶(ACE)催化形成具有活性的八肽:血管紧张素Ⅱ,过度激活RAS产生的血管紧张素Ⅱ将主要通过血管紧张素Ⅱ受体1型(AT1R)产生高血压及靶器官损害.     

Anti-malarial efficacy of pyronaridine and artesunate in combination in vitro and in vivo

Pyronaridine is a Mannich base anti-malarial with demonstrated efficacy against drug resistant Plasmodium falciparum, P. vivax, P. ovale and P. malariae. However, resistance to pyronaridine can develop quickly when it is used alone but can be considerably delayed when it is administered with artesunate in rodent malaria models. The aim of this study was to evaluate the efficacy of pyronaridine in combination with artesunate against P. falciparum in vitro and in rodent malaria models in vivo to support its clinical application. Pyronaridine showed consistently high levels of in vitro activity against a panel of six P. falciparum drug-sensitive and resistant strains (Geometric Mean IC50=2.24 nM, 95% CI=1.20-3.27). In vitro interactions between pyronaridine and artesunate showed a slight antagonistic trend, but in vivo compared to pyronaridine and artesunate administered alone, the 3:1 ratio of the combination, reduced the ED90 of artesunate by approximately 15.6-fold in a pyronaridine-resistant P. berghei line and by approximately 200-fold in an artesunate-resistant line of P. berghei. Complete cure rates were achieved with doses of the combination above or equal to 8 mg/kg per day against P. chabaudi AS. These results indicate that the combination had an enhanced effect over monotherapy and lower daily doses of artesunate could be used to obtain a curative effect. The data suggest that the combination of pyronaridine and artesunate should have potential in areas of multi-drug resistant malaria.     

Modulation of enterotoxin binding and function in vitro and in vivo

The use of the nontoxic B subunits of cholera and Escherichia coli enterotoxins in vitro and in vivo led to a decrease in toxin binding to target cells and a decrease in toxin-induced effects (i.e., morphological effects, adenylate cyclase activation, and fluid secretion). The reduction in toxin binding involves a process of down-regulation of cellular receptors for the toxin and not toxin occupancy of receptors. The extent of inhibition was dependent on the amount of B subunit used and on the duration of time after its use. Thus, in vivo exposure to a single bolus of B subunit was sufficient to block toxin binding and activity for up to 18 h. Because the B subunit binds extensively to the esophagus and the stomach, peroral administration will require a preparation that allows the subunit to reach the small bowel in a protected form. Our data provide a rationale for using B subunit therapy for short-term protection against the effects of enterotoxins, before the development of an immune response.     

我国高血压防治现状和策略

<正>我国现患高血压2亿人,由于人群高血压患病率的不断升高和防控力度不够,我国高血压人群的知晓率、治疗率、控制率仍处于较低水平。对于像高血压这样的群体性慢性病,应当采取全人     

Cooperation of B- and T-lymphocytes of the human in vitro and in vivo

It is reported on the experimental proofs for the existence of a cooperation of different populations of lymphocytes in man. Regulatory lymphocytes play a part in the regulation of the synthesis of immunoglobulins by polyclonally stimulated B-lymphocytes, in the generation of killer-T-cells and in the regulation of the DNA-synthesis by mitogenically stimulated T- and B-cells. Typical helper- and suppressor-effects may be proved. Disturbances of lymphocytic interactions may be a cause for the development of immune deficiency diseases. It is very probable that also in several chronic infections a dysfunction of regulatory T-lymphocytes is present.     

Uptake of labeled alloxan in mouse organs and mitochondria in vivo and in vitro

[14C]2-Alloxan was administered in vivo and in vitro for study of the uptake of alloxan in different organs and their mitochondia of mice. After in vivo administration, radioactivity was demonstrated in all organs investigated, with quantitative differences: endocrine pancreas greater than liver greater than exocrine pancreas and heart. No significant difference was found between the iv and ip routes of injection. An in vivo uptake of alloxan was also found in mitochondria, with significant quantitative differences as to the origin of the organelles: endocrine pancreas greater than liver greater than exocrine pancreas and heart. Pretreatment with D-glucose caused significantly decreased uptake in liver, exocrine pancreas, and heart, but significantly increased uptake in endocrine pancreas, whereas the uptake was significantly decreased in the mitochondria from all of these organs. In vitro uptake was observed in all kinds of mitochondria studied. This uptake was higher than the in vivo uptake in mitochondria from liver, exocrine pancreas, and heart, whereas the uptake in vivo was higher than the in vitro uptake in islet mitochondria. The presence of D-glucose did not affect the in vitro uptake of alloxan in mitochondria. The findings show that in vivo, alloxan passes across plasma membranes and is taken up by mitochondria, and data obtained with mitochondrial subfractions may also indicate a passage across mitochondrial membranes. D-Glucose protection against alloxan diabetogenicity may be associated with prevention of mitochondrial uptake of alloxan. This prevention seems to be dependent on the metabolism of glucose.