卡托普利对自发性高血压大鼠心血管组织肾素、血管紧张素的影响

为研究卡托普利（ＣＡＰ）对心血管组织肾素─血管紧张素系统的影响，５周龄雄性卒中型自发性高血压大鼠（ＳＨＲｓｐ）随机分为实验组（ｎ＝１２）及对照组（ｎ＝８），分别于食管内喂饲ＣＡＰ（６０ｍｇ·ｋｇ－１／ｄ）或蒸馏水，每日１次，持续８周。用放射免疫法测定血浆肾素活性、血管紧张素Ⅱ（ＡｎｇⅡ），心肌和主动脉平滑肌（ＡＳＭ）的肾素浓度（ＲＣ）和ＡｎｇⅡ含量。结果显示，实验组血压不升高，心室重／体重比值也低于对照组；心肌和ＡＳＭ的ＲＣ比对照组高；而ＡｎｇⅡ被明显抑制，分别为７．０２±０．９６比１３．４０±５．３９（Ｐ＜０．０１）和２４．８０±４．９３比３３．６５±８．８９ｐｇ／ｍｇ蛋白（Ｐ＜０．０２）。这说明，ＣＡＰ长期治疗可明显阻止ＳＨＲｓｐ的血压上升及心肌肥厚的发生，降低心肌和ＡＳＭ中ＡｎｇⅡ含量，提示在这种模型，ＣＡＰ降压及抗心肌肥厚的重要机制之一是阻断心血管组织局部ＡｎｇⅡ的生成。     

氢氯噻嗪分别与氯沙坦或卡托普利联合应用的降压疗效和安全性的比较观察

目的:比较联合应用氯沙坦和氢氯噻嗪与卡托普利和氢氯噻嗪治疗高血压的疗效和安全性。方法:72例新诊断或经2周洗脱期后基线平均舒张压为95～115mmHg,平均收缩压<180mmHg的高血压病患者,随机分成A、B两组各36例。A组每天服用氯沙坦50mg和氢氯噻嗪12.5mg,B组每天服用卡托普利50mg和氢氯噻嗪25mg。用药后每周测血压,以基线值与第4周末血压的平均变化作为疗效指标,并记录药物不良反应,结合实验室检查结果作安全性评估。结果:两治疗组第4周平均舒张压及平均收缩压降低无显著差异(P>0.10)。但与药物相关的不良反应A组显著低于B组(8.4％对16.7％)。结论:联合应用氯沙坦和氢氯噻嗪与卡托普利和氢氯噻嗪降压疗效相似,但前者的安全性和耐受性较好。     

高静水压对内皮细胞一氧化氮合酶抑制物的影响及卡托普利的干预作用

目的 :观察高静水压培养的人脐静脉内皮细胞 (HUVECs)内源性一氧化氮 (NO)合酶抑制物———不对称二甲精氨酸 (ADMA)的影响及卡托普利的保护作用。方法 :采用改良的Jaffe法培养原代HUVECs,取生长良好的3～ 6代HUVECs用于实验 ,分为①大气压组 :加等量DMEM培养液 ;②高静水压组 ;③高压加卡托普利组。测定上清液中ADMA、左旋精氨酸 (L arg)、NO和内皮素 (ET)的浓度 ,并测定血管紧张素转化酶 (ACE)的活性。结果 :高静水压组ADMA、ET的量、细胞内钙 [Ca2 + ]i及ACE活性增加 ,而NO的量减少。卡托普利干预后 ,上清液中ADMA、ET的浓度减少 ,ACE活性降低 ,NO的量增加 ,而L arg水平无明显变化。结论 :高静水压通过增加ADMA导致内皮功能紊乱 ,卡托普利则能通过减少ADMA减轻高压导致的内皮细胞代谢功能障碍     

Captopril and ramiprilat protect against free radical injury in isolated working rat hearts

The protection of angiotensin converting enzyme (ACE) inhibitors, captopril and ramiprilat, against free radical-mediated myocardial injury were studied in isolated working rat hearts. Free radicals were generated by electrolysis of Krebs-Henseleit solution with 10 mA direct current for 1 min. Both captopril (360 μmol/l) and ramiprilat (12.5 μmol/l) significantly reduced the decrease of left ventricle dP/dt′_max, coronary flow (CF), myocardial superoxide dismutase (SOD) and creatine kinase (CK) activities and the elevation of S-T segment of epicardial ECG as well as the rise of myocardial malondialdehyde (MDA) content caused by electrolysed perfusate. Captopril afforded a dose-dependent protection on cardiac functions with various concentrations of 45, 90, 180 and 360 μmol/l. Iloprost (30 nmol/l), a stable mimetic of prostacyclin, could also alleviate free radical-mediated myocardial injuries. All the beneficial effects of ramiprilat (12.5 μmol/l) were abolished by the administration of indomethacin (5 μmol). In contrast, captopril (90 μmol/l) still exhibited significant protective effects after indomethacin (9 μmol) was administered, though these protective effects were insignificantly weakened. In order to assess the role of sulfhydryl (-SH) group in the effects of captopril, a SH-containing drug S8 and a disulfide DG4, both are deficient in ACE inhibitory properties in vitro, were examined. Data showed that S8 (180 μmol/l) provided a significant protection while DG4 showed no protective effect. It is concluded that ACE inhibitors can protect against free radical-induced myocardial damage. Ramiprilat, a non-SH-containing ACE inhibitor, inhibits free radical-induced damages mainly by stimulation of prostacyclin synthesis and/or release. In addition to this effect, captopril, a SH-containing ACE inhibitor, may exert additional anti-free radical effects by a mechanism which is probably related to the sulfhydryl group.     

卡托普利对非酒精性脂肪性肝病大鼠肝细胞脂肪变性的影响

目的 研究卡托普利对非酒精性脂肪性肝病(NAFLD)大鼠肝细胞脂肪变性的影响。方法 随机将64只大鼠分为对照组16只(普通饲料喂养和生理盐水灌胃)、模型组16只(高脂饲料和生理盐水灌胃)、卡托普利处理组16只和罗格列酮处理组16只。给药6 w后取血清和肝组织,检测肝组织细胞色素氧化酶P4502E1(CYP2E1)mRNA水平及血清丙二醛(MDA)和谷胱甘肽(GSH)水平。结果 模型组肝细胞体积增大,见广泛性脂肪变性和细胞水肿,而卡托普利处理组大部分肝细胞排列正常,可见少量的脂肪变性,部分细胞水肿;卡托普利处理组血清AST、ALT、TC和TG水平分别为(94.1±15.6)U/L、(27.3±6.2)U/L、(1.4±0.2)mmol/L和(1.0±0.2)mmol/L,显著低于模型组【分别为(134.4±35.1)U/L、(35.2±7.1)U/L、(1.8±0.4)mmol/L和(1.4±0.2)mmol/L,P＜0.05】;卡托普利处理组肝湿重、肝指数和肝组织CYP2E1 mRNA水平分别为(11.7±2.1)g、(2.3±0.3)%和(1.8±0.2),显著低于模型组【分别为(14.3±2.0)g、(2.6±0.2)%和(2.3±0.1),P＜0.05】;卡托普利处理组血清MDA水平为(7.6±2.5)nmol/L,显著低于模型组【(12.1±2.6)nmol/L,P＜0.05】,而血清GSH水平为(41.0±17.5)mg/L,显著高于模型组【(22.2±10.2)mg/L,P＜0.05】。结论 卡托普利可有效减轻非酒精性脂肪性肝病大鼠肝细胞脂肪变性程度,可能与纠正脂代谢紊乱、恢复肝功能、增强抗氧化应激能力有关。     

Effect of captopril on serum TNF-α level in acute lung injury rats induced by HCL

Objective:To observe the effect of captopril on the tumor necrosis factor-α(TNF- α) level and arterial blood gases in acute lung injury(All) induced by HCL in rats,and to analyze its protective mechanism.Methods:Fifty Wistar rats were selected and randomly divided into three groups,with 20 rats in Group Ⅰ and Ⅱ,respectively and 10 animals in Group Ⅲ.ALI model was constructed by intratracheal injection of diluted hydrochloric acid(pH=1.25.1.2 mL/kg).Group Ⅰrats received not any treatment after construction of AM model.Group Ⅱ rats were treated with captopril(5 mg/kg,i.p.) 5 min after induction of ALI.Group Ⅲ served as normal control without any treatment.Ninety minutes after construction of ALI model,all the rats were sacrificed.Blood was withdrawn for detection of TNF- α level and arterial blood gases index.And lung tissue slices of the three groups were prepared for observation of pathologic histology changes.Results:TNF- α level in serum of Group Ⅰ and Ⅱ rats was significantly higher than that in Group Ⅲ(P0.05),while TNF- α level in serum of Group Ⅱ was significantly lower in Group Ⅰ(P0.05).PaCO_2 level was significantly higher(P0.05),while PaO_2 was significantly lower(P0.05) in Group Ⅰ and Ⅱ rats than those in Group Ⅲ.PaCO_2 was significantly lower(P0.05) and PaO_2 was significantly higher(P0.05) in Group Ⅱ than those in Group Ⅰ.Histological observation showed diffuse congestion and severe edema of luug tissue,obvious thickening and structure damage of alveolar walls and a large amount of neutrophil infiltration in Group Ⅰ rats.Group Ⅱ rats showed mild edema of lung tissue;only a small portion of alveolar walls showed thickening and only a few of neutrophil infiltration could be observed.The degree of injury was remarkably slighter than that of Group Ⅰ rats.Group Ⅲ rats showed clear lung tissue structure and normal morphology:alveolar walls were uniform and the margin was smooth and few neutrophil could be observed.Conclusions:Captopril can significantly reduce serum TNF- α level,elevate PaO_2 and reduce PaCO_2 in rats with ALI.It has a protective effect on ALI rats.     

复方卡托普利片中未知杂质的来源与结构分析

目的 对复方卡托普利片中新发现的未知杂质进行来源分析和结构的初步确认,以期为该制剂改进工艺和提高标准提供依据。方法 采用Kromasil苯基色谱柱（250 mm×4.6 mm,5 μm）,以水-磷酸（550︰0.5）和甲醇为流动相进行梯度洗脱,检测波长为210 nm。对市售的复方卡托普利片中的该未知杂质的含量进行系统的评价;同时采用液质联用的方法对该未知杂质的结构进行确认。结果 该未知杂质为复方制剂的2种原料卡托普利和氢氯噻嗪在受热过程中产生的二聚物,分子式为C₁₆H₂₃N₄O₇S₃Cl;市售产品多数含有该杂质。结论 本研究为复方卡托普利片的质量控制和工艺优化提供了参考依据。     

酮酸片联合卡托普利治疗糖尿病肾病临床蛋白尿的效果研究

目的 了解酮酸片联合卡托普利治疗糖尿病肾病临床蛋白尿的临床效果.方法 对2011年12月至2013年12月收治的确诊为糖尿病肾病临床蛋白尿患者进行抽样,选取100例患者随机分成两组进行对比观察,其中对照组予以胰岛素强化血糖控制,口服卡托普利,实验组在强化血糖控制的基础上加以复方α-酮酸片进行治疗,比较两组患者尿蛋白排泄量、血浆清蛋白量与临床治疗效果.结果 总有效率实验组（98％）显著优于对照组（82％）,两组比较差异具有统计学意义（P＜0.05）.实验组16例24h尿蛋白定量＜0.5 g/L,3例为0.5～1.0 g/L;对照组15例24 h尿蛋白定量＜0.5 g/L,4例为0.5 ～ 1.0 g/L;实验组1例血浆清蛋白量＜25g/L,对照组2例,两组比较差异有统计学意义（P＜0.05）.结论 针对糖尿病肾病临床蛋白尿患者而言,基于低蛋白饮食与血脂、血糖、血压控制等治疗基础上,采用复方α-酮酸片联合卡托普利进行治疗,有助于减少蛋白尿,控制糖尿病肾病进展.     

硝苯地平联合卡托普利治疗原发性高血压的临床效果分析

目的观察研究硝苯地平联合卡托普利治疗原发性高血压的临床效果。方法将入住本院心血管内科并已确诊为原发性高血压的136例患者随机分为观察组68例和对照组68例。观察组患者进行使用硝苯地平控释片和卡托普利治疗,对照组患者服用卡托普利进行治疗。系统治疗8周后,评价两组患者的临床效果。结果观察组的总有效率为92．65％,对照组为75．00％,观察组的疗效明显优于对照组（P〈0．05）。观察组的舒张压和收缩压均明显低于对照组,两组差异有统计学的意义（P〈0．05）。结论硝苯地平联合卡托普利治疗原发性高血压的效果优于与单独服用卡托普利。     

卡托普利对动脉损伤后内膜增生时纤溶系统的影响

目的　通过兔颈总动脉球囊损伤模型 ,观察卡托普利 (开搏通 ,captopril)对动脉球囊损伤后内膜增生时纤溶系统的影响。方法　以兔右颈总动脉内膜剥脱为实验模型 ,36只兔随机分为假手术组 (对照组 )、单纯损伤组、损伤 +药物治疗组 (简称药物治疗组 ) ,每组各 12只。药物治疗组术前1d至术后 30d给予captopril2mg·kg 1 ·d 1 ,余二组不给药 ,用ELISA法检测各组术前、术后 1、3、7、14、30d的血浆组织纤溶酶原激活剂 (t PA)、纤溶酶原激活剂抑制物 1(PAI 1)的水平 ,并于术后 30d行病理形态学观察各组血管内膜厚度及管腔狭窄度。结果　动脉球囊损伤后 ,药物治疗组PAI 1水平、内膜的厚度及管腔狭窄度均明显低于单纯损伤组。结论　血管球囊损伤术后纤溶系统作用的减弱影响动脉壁损伤再修复过程 ,captopril可使纤溶系统保持平衡 ,预防血管成形术后再狭窄。