四逆汤(附子、干姜、甘草)对肾血管性高血压大鼠血压调节作用的实验研究

目的探讨四逆汤对肾血管性高血压大鼠血压的调节作用和可能的机制。方法健康雌性Wistar大鼠24只,随机分为正常组、对照组和治疗组,每组8只。根据双肾动脉夹闭法建立肾性高血压动物模型,应用四逆汤(附子、干姜、甘草)灌胃治疗2周,RBF-2型鼠尾动脉血压计测量血压,放射免疫法测定血浆中血管紧张素Ⅱ(AngⅡ)和降钙素基因相关肽(CGRP)的含量,TUNEL法检测肾组织细胞凋亡,免疫组化法测定肾组织中AngⅡ和CGRP的表达。结果(1)对照组和治疗组大鼠血压较正常组明显升高,四逆汤能明显降低血压[(131.6±14.2vs116.2±8.3)mmHg,P<0.05]。(2)各组动物血浆AngⅡ水平无显著性变化(P>0.05),治疗组CGRP含量较对照组明显升高[(75.2±12.2vs54.8±18.1)pg/mL,P<0.05]。(3)四逆汤治疗明显减少肾小球凋亡阳性细胞数(12.6±3.5vs29.4±3.5细胞个数/10个视野,P<0.05);治疗组明显降低AngⅡ表达水平,显著升高CGRP表达水平(P<0.05)。结论四逆汤可能通过调节肾血管性高血压大鼠血浆和肾组织中血管活性物质AngⅡ和CGRP的水平,发挥其血压调节和保护高血压靶器官的作用。     

肾性高血压大鼠血浆中降钙素基因相关肽与血管紧张素Ⅱ浓度及肾素活性的变化

降钙素基因相关肽与肾素－血管紧张素系统均参与血压的调节。在两肾一夹型肾性高血压大鼠模型，观察大鼠血浆中的降钙素基因相关肽、血管紧张素Ⅱ浓度及肾素活性的水平，以及用氯沙坦或培哚普利干预后这些活性肽在血浆中的变化，进一步分析这些血管活性肽在该模型的变化机制。研究显示，高血压组血浆中降钙素基因相关肽的浓度高于对照组，而血管紧张素Ⅱ与对照组相比无显著差异。用氯沙坦和培哚普利治疗6周后，血浆中肾素活性和血管紧张素Ⅱ及降钙素基因相关肽水平均升高。本研究发现在肾性高血压中期，循环中肾素－血管紧张素系统对血压的影响已不是主要因素，降钙素基因相关肽的释放增加可能是血压升高的代偿作用。应用氯沙坦和培哚普利后可增加血浆中血管紧张素Ⅱ浓度和肾素活性，同时也增加降钙素基因相关肽的合成与释放，这可能对其降压起一定的作用。     

金线莲提取物RM对肾血管性高血压大鼠的血压及血管紧张素Ⅱ的影响

目的:观察金线莲提取物RM对肾血管性高血压大鼠(RHR)血压和血浆血管紧张素Ⅱ(AngⅡ)含量的影响。方法:应用二肾一夹法制作RHR模型。RM单次股静脉注射给药,给药前后以颈总动脉插管连接多媒体生物信号记录系统测定大鼠动脉血压和心率;以放射免疫法测血浆AngⅡ含量。结果:金线莲提取物RM显著降低RHR的收缩压、舒张压,减慢心率和降低血浆AngⅡ含量,并呈剂量依赖性关系(P<0.05~<0.01)。RM给药30 min后,降低血压、心率效果最著(P<0.01)。结论:金线莲提取物RM对肾血管性高血压大鼠具有良好的降压作用,其降压机制可能与降低AngⅡ的含量有关。     

肾性高血压大鼠血浆中降钙素基因相关肽与血管紧张素Ⅱ浓度及肾素活性的变化

降钙素基因相关肽与肾素-血管紧张素系统均参与血压的调节.在两肾一夹型肾性高血压大鼠模型,观察大鼠血浆中的降钙素基因相关肽、血管紧张素Ⅱ浓度及肾素活性的水平,以及用氯沙坦或培哚普利干预后这些活性肽在血浆中的变化,进一步分析这些血管活性肽在该模型的变化机制.研究显示,高血压组血浆中降钙素基因相关肽的浓度高于对照组,而血管紧张素Ⅱ与对照组相比无显著差异.用氯沙坦和培哚普利治疗6周后,血浆中肾素活性和血管紧张素Ⅱ及降钙素基因相关肽水平均升高.本研究发现在肾性高血压中期,循环中肾素-血管紧张素系统对血压的影响已不是主要因素,降钙素基因相关肽的释放增加可能是血压升高的代偿作用.应用氯沙坦和培哚普利后可增加血浆中血管紧张素Ⅱ浓度和肾素活性,同时也增加降钙素基因相关肽的合成与释放,这可能对其降压起一定的作用.     

气体信使硫化氢在大鼠肾血管性高血压中的调节作用

目的探讨硫化氢体系在肾血管性高血压形成及发展中的变化和作用。方法成年的雄性Wistar大鼠28只,随机分为对照组7只、双肾一夹组(two-kidney,one-clip,2KIC组)7只、2KIC+硫氢化钠(硫氢化钠为外源性硫化氢供者)组8只、假手术组6只,其中2KIC+硫氢化钠组每天腹腔注射硫氢化钠(56μmol/kg),对照组、2KIC组及假手术组注射相同剂量的生理盐水。相同条件饲养4周,4周后处死,检测血浆硫化氢水平,双肾硫化氢合酶的活性,血管紧张素Ⅱ,左心与全心重量比,光学显微镜下观察肾的显微结构变化。结果术后4周,2KIC组尾动脉压显著高于假手术组及2KIC+硫氢化钠组;2KIC组的血管紧张素Ⅱ显著高于假手术组和对照组;左心室与全心重量比值2KIC组高于对照组和假手术组;肾内硫化氢合酶的活性及血浆中硫化氢的含量2KIC组显著低于假手术组及对照组,2KIC+硫氢化钠组高于2KIC组。结论肾血管性高血压大鼠硫化氢体系受到严重抑制,可能是肾性高血压形成的重要因素,外源性的给予硫化氢供者有助于缓解高血压的形成。     

Apelin在肾血管性高血压大鼠模型中的浓度及意义

目的观察Apelin在肾血管性高血压大鼠模型中的含量以及与血管紧张素Ⅱ(AngⅡ)、一氧化氮(NO)的相关性,探讨Apelin在肾血管性高血压中的作用。方法将20只雄性180～220gWistar大鼠随机分为手术组和假手术组。在术后4周测量平均颈动脉压,确定模型制备成功。ELISA法测定血浆Apelin-12、AngⅡ、NO浓度,分析其相关性;免疫组化法检测心脏Apelin-12蛋白表达。分析手术组与假手术组平均颈动脉压、血浆Apelin-12、AngⅡ、NO浓度变化和心脏组织Apelin-12表达情况。结果平均颈动脉压手术组与假手术组相比显著增高(P<0.01)。血浆中Apelin-12及AngⅡ浓度手术组高于假手术组(P<0.01);血浆中NO浓度手术组低于假手术组(P<0.01)。心脏组织中Apelin-12蛋白表达手术组高于假手术组。手术组血浆中Apelin-12浓度与AngⅡ浓度呈正相关(r=0.877,P<0.01),与NO浓度呈负相关(r=-0.853,P<0.01)。结论 Apelin-12可能在肾血管性高血压的病理生理发展过程中发挥作用。Apelin-12、AngⅡ、NO共同参与肾血管性高血压的发生发展过程,Apelin-12可能通过AngⅡ、NO发挥作用。     

金线莲提取物ARL对肾血管性高血压大鼠血压、血管紧张素Ⅱ、一氧化氮和内皮素的影响

目的观察金线莲提取物ARL对肾血管性高血压大鼠(RHR)血压、血浆血管紧张素Ⅱ(AngⅡ)、内皮素(ET-1)和血清一氧化氮(NO)、一氧化氮合酶(NOS)浓度的影响。方法应用二肾一夹法制作RHR模型。ARL灌胃给药15 d,给药后第5、10、15天以大鼠尾动脉测压法测量清醒 RHR收缩压及心率。给药第15天末处死动物取血,放射免疫法测AngⅡ、ET-1浓度,硝酸还原酶法、生物化学法分别测定血清NO、NOS浓度。结果ARL灌胃给药5 d后,RHR的血压和心率较给药前明显降低。ARL给药15 d后,RHR血清NO、NOS的含量明显增加、血浆ET-1、AngⅡ的含量明显降低。结论ARL对肾血管性高血压大鼠具有良好的降压作用,其降压机制可能与降低ET-1、AngⅡ升高NO的含量有关。     

肾血管性高血压的若干认识

肾血管性高血压是各种原因引起的肾动脉入口、主干或其主要分支狭窄，引起肾实质缺血产生的继发性高血压。肾素-血管紧张素系统（RAS）、血管内皮功能障碍等多种因素参与发病过程。肾血管性高血压一方面可以导致心、脑、肾等多种靶器官损害；另一方面，早期诊断，及时治疗，病变在一定程度上具有可逆性，因而日趋受临床医生的重视。本文就肾血管性高血压流行病学，病理生理改变，治疗等方面进展作一综述。     

四逆汤对肾性高血压大鼠主要靶器官血管活性物质表达的影响

目的研究四逆汤对肾性高血压大鼠主要靶器官血管活性物质表达的影响。方法健康雌性Wistar大鼠24只，随机分为正常对照组、肾性高血压组和四逆汤治疗组，每组8只。根据双肾动脉夹闭法建立肾性高血压动物模型，免疫组化法测定心、脑、肾组织内皮素受体A（ETRA）、一氧化氮合酶（NOS）、血管紧张素Ⅱ（Ang—Ⅱ）、降钙素基因相关肽（CGRP）的表达。结果①各靶器官ETRA表达水平，肾性高血雎组均显著高于正常对照组（P〈O．05）；四逆汤治疗组在肾和心均显著低于肾性高血压组（P〈0．05），但在脑无显著性差异（P〉0．05）。②肾和脑iNOS表达水平，肾性高血压组显著高于正常对照组（P〈0．05）；四逆汤治疗组明显低于肾性高血压组（P〈0．01）。心脏eNOS表达水平，肾性高血压组显著低于正常对照组（P〈0．01），治疗组显著高于高血压组（P〈0．01）。③各器官CGRP表达水平，肾性商血压组较正常对照组均显著升高（P〈0．05）；四逆汤治疗组较肾性高血压组均明显降低（P〈0．01）；④Ang—Ⅱ在肾和心的表达水平，四逆汤治疗纰较肾性高血压组均明显降低（P〈0．05），但在脑无显著性差异（P〉0.05）。结论四逆汤可能通过调节肾性高血压大鼠肾、心、脑组织中ETRA、NOS、Ang—Ⅱ和CGRP的表达水平，发挥其血压调节作用。     

人工寒潮对易卒中型肾血管性高血压大鼠内皮素及降钙素基因相关肽的影响

目的探讨人工寒潮对易卒中型肾血管性高血压大鼠内皮素及降钙素基因相关肽(CGRP)影响的研究。方法选择健康雄性SD大鼠72只,其中模型组36只,对照组36只。将2组大鼠置于人工寒潮环境中,分别将寒潮前、寒潮3、6、12h及寒潮后12、24h大鼠麻醉,每时间点6只。取嘴侧至尾侧1.5mm脑片进行内皮素、CGRP检测,原位杂交检测内皮素mRNA表达。结果模型组寒潮前,寒潮3、6、12h及寒潮后12、24h内皮素和内皮素mRNA表达明显高于对照组,寒潮前及寒潮后24hCGRP表达明显低于对照组,差异有统计学意义(P0.05)。模型组寒潮3、6h内皮素和CGRP表达较寒潮前明显升高,差异有统计学意义(P0.05)。模型组寒潮3、6、12h内皮素mRNA表达较寒潮前明显升高(28.00±6.02、27.06±5.46、26.40±4.60 vs 22.81±4.35,P0.05)。结论寒潮时易卒中型肾血管性高血压大鼠内皮素及CGRP增加,与寒冷时脑卒中的发生有一定的关系。     

哇巴因抗体对肾血管性高血压大鼠的降压作用

目的：探讨哇巴因抗体的降压作用及内源性哇巴因与高血压发病的关系。方法：给”一肾一夹（１Ｋ１Ｃ）“”两肾一夹＋盐（２Ｋ１Ｃ－ｓａｌｔ）”肾血性高血压大鼠随机静注哇巴因抗体、硝普钠、正常兔免疫球蛋白（ＩｇＧ）及生理盐水,颈动脉插管观察注射生３小时内大鼠血压的动态变化。结果：哇巴因抗体对“一肾一夹”、“两肾一夹＋盐”型高血压大鼠具有明显的降压作用,而对“两肾一夹”高血压鼠降压作用不明显。正常免免疫球蛋白     

Effect of γ-Tocotreenol on Blood Pressure,Lipid Peroxtoation and Total Antioxtoant Status in Spontaneously Hypertensive Rats (SHR)

The aim of this study was to determine the effects of γ tocotrienol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar Kyoto (WKY) rats.

SHR were divided into three groups and treated with different doses of γ tocotrienol (γl, 15mg/kg diet; γ2, 30mg/kg diet and γ3, 150mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressure were recorded every fortnightly for three months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity and lipid peroxide levels in plasma and blood vessels were carried out following well established methods.

Study shows that lipid peroxides were significantly higher in hypertensive plasma and blood vessels compared to that of normal rats (Plasma- N: 0.06±0.01, HC: 0.13±0.008;     

Open-Field Behaviour and Blood Pressure in Spontaneously Hypertensive Rats

The relation between the development of hypertension and changes in behaviour was investigated. Open-field activity of male and female Spontaneously Hypertensive Rats (SHR) and Wistar-Kyoto controls (WKY) was scored at 4, 6 or 10 weeks of age. SHR generally showed higher locomotor activity and exploratory rearing behaviour, but lower grooming activity and defecation. These changes were found for rearing (3–5 fold increase) and grooming scores at all ages, ambulation at 4 weeks and 10 weeks (ambu-lation-inner) and defecation at 6 and 10 weeks of age. Differences were generally more pronounced in female rats. SHR showed less habituation than WKY. Already at the age of 4 and 6 weeks blood pressure was increased in SHR compared with WKY (approximately 120 mm Hg vs. 100 mm Hg). Between 6 and 10 weeks of age blood pressure increased rapidly in SHR, leading to a marked difference at the latter age (about 40 mm Hg), in both male and female rats.

These experiments show that already at a young age, when blood pressure differences with WKY are small, marked behavioural changes are present in SHR. The altered behaviour could play a role in the development of hypertension in SHR.     

Apelin Effects on Blood Pressure and RAS in DOCA-Salt-Induced Hypertensive Rats

Apelin, a novel multifunctional peptide implicated in the regulation of the cardiovascular system, including blood pressure and cardiac function control, has been postulated to be involved in the pathophysiology of hypertension and hypertensive heart disease. The aim of this study was to investigate, for the first time, whether the effects of apelin’s chronic application might be involved in deoxycorticosterone acetate-salt-induced hypertensive rats (DOCA-salt rats). In this study, 8–10-week-old male Wistar rats were divided into four groups: control, control + apelin, DOCA-salt rats, DOCA-salt rats + apelin. Deoxycorticosterone Acetate (25 mg/kg of body weight) was injected subcutaneously, twice a week for 4 weeks. These rats received NaCl 1% instead of tap water for drinking during the experimental period. Later, rats were randomly treated with pyroglutamylated apelin-13 (200 μg. kg^?1. day^?1 intraperitonealy) for 17 days. The concentrations of apelin, endothelin-1, angiotensin-converting enzyme, angiotensinogen, and angiotensin II were analyzed in the plasma. The mRNA level of apelin and apelin receptor were determined in the heart and aorta tissue by real-time polymerase chain reaction, respectively. It was found that apelin reduces blood pressure in DOCA-salt rats. Apelin can be used as a therapeutic agent in the treatment of hypertension in the future.     

哇巴因抗体对肾血管性高血压大鼠的降压作用

目的:探讨哇巴因抗体的降压作用及内源性哇巴因与高血压发病的关系.方法:给"一肾一夹(1K1C)"、"两肾一夹+盐(2K1C-salt)"及"两肾一夹(2K1C)"肾血管性高血压大鼠随机静注哇巴因抗体、硝普钠、正常兔免疫球蛋白(IgG)及生理盐水,颈动脉插管观察注射后3 小时内大鼠血压的动态变化. 结果:哇巴因抗体对"一肾一夹"、"两肾一夹+盐"型高血压大鼠具有明显的降压作用,而对"两肾一夹"高血压鼠降压作用不明显.正常兔免疫球蛋白对各种高血压模型均无降压作用.结论:哇巴因抗体对"一肾一夹"、"两肾一夹+盐 "型高血压大鼠具有降压作用,间接证明了内源性哇巴因可能是高血压的发病因素之一.     

肾血管性高血压大鼠心肌纤维化发展过程的实验研究

采用二肾一夹肾血管性高血压（２Ｋ１Ｃ－ＲＨＴ）大鼠为模型，观察在反应性和修复性纤维化阶段心肌胶原形态和生化的改变。方法建立２Ｋ１Ｃ－ＲＨＴ模型，将大鼠随机分为４组：术后４，１２周高血压组和对照组。苦味酸天狼星红染色观察胶原形态，图像分析系统测量胶原容积分数（ＣＶＦ）和血管周围胶原面积（ＰＶＣＡ），羟脯氨酸法测定心肌胶原浓度（Ｃｏｌ）。结果在反应性纤维化阶段，心肌胶原从血管周围向邻近间质短距离延伸，同时ＣＶＦ、ＰＶＣＡ和Ｃｏｌ显著增高；在修复性纤维化阶段，胶原在间质中长距离延伸，出现取代缺失心肌细胞的疤痕灶，同时ＣＶＦ、ＰＶＣＡ和Ｃｏｌ进一步升高。结论提示２Ｋ１Ｃ－ＲＨＴ大鼠心肌纤维化呈进行性发展。     

Dietary L-Arginine Attenuates Blood Pressure in Mineralocorticoid-Salt Hypertensive Rats

The present study was designed to investigate the influence of dietary L-arginine supplementation on blood pressure and on ex vivo vascular reactivity in mineralocorticoid-salt (DOCA-salt) hypertensive rats. Systolic blood pressure and heart rate were determined throughout the experimental period in unanaesthetized rats. Plasma and urine electrolyte levels were measured. Vasoconstrictor response to noradrenaline and vasodilator responses to acetylcholine and sodium nitroprusside were evaluated in the isolated perfused mesenteric vascular bed. DOCA-salt hypertensive rats were divided into 2 groups: a control group and a treated group receiving 0.8% L-arginine supplementation in drinking water. Dietary L-arginine supplementation attenuated systolic blood pressure in conscious DOCA-salt hypertensive rats, but did not modify heart rate. Plasma calcium and sodium concentrations and urinary magnesium excretion were decreased by L-arginine supplementation. Noradrenaline-induced vasoconstriction decreased and acetylcholine-induced vasodilatation increased, whereas sodium nitroprusside-induced vasodilatation was not modified, in the L-arginine-supplemented rats. It is concluded that dietary L-arginine supplementation in the diet lowers systolic blood pressure in DOCA-salt hypertensive rats, probably through vascular action.