高效毛细管电泳测定血管紧张素转化酶抑制剂captopril的活性

目的 建立高效毛细管电泳测定血管紧张素转化酶抑制剂captopril抑制活性的方法。方法 用紫外分光光度计确定了马尿酸的特征吸收波长为 2 2 8nm。高效毛细管电泳的条件 :熔融石英毛细柱 ,电泳缓冲液为pH 8 3的5 0mmol·L- 1 磷酸缓冲液 ,进样压力 4 8kPa,进样时间 3s,分离电压 2 0kV ,检测波长 2 2 8nm。结果 在 7min内使反应物和生成物完全分离 ,标定了captopril的IC50 值为 0 0 19μmol·L- 1 ,经过酶反应动力学判断captopril为竞争性抑制剂。结论 该方法准确、简便、快速 。

大鼠过度训练时RAS的变化意义及Captopril的保护作用

雄性Ｗｉｓｔａｒ大鼠随机分成４组：（１）对照（Ｃ）组；（２）一般游泳训练（ＮＳ）组；（３）过度负荷（Ｏ）组；（４）过度负荷＋Ｃａｐｔｏｐｒｉｌ（ＯＣ）组。游泳训练共8周，建立模拟过度训练动物模型。测定了各组肾素－血管紧张素（ＲＡＳ）活性，并对心肌细胞线粒体钙含量、丙二醛（ＭＤＡ）含量、膜荧光偏振度值、血清肌钙蛋白（ＴｎＴ）含量以及心肌组织ＨＥ染色光镜等指标进行了探讨。对ＲＡＳ各主要成分研究表明，在过度训练状态下，循环和心脏局部ＲＡＳ异常活跃，大鼠心肌发生严重损害是个别现象，大鼠心肌存在钙过载和线粒体膜自由基损伤，上述三者之间有密切相互关系。提示ＲＡＳ在过度训练心肌损害中有重要意义，使用Ｃａｐｔｏｐｒｉｌ后对心肌损害有保护作用。

短期大强度训练对大鼠心脏超微结构和功能变化的影响及Captopril的调节作用

目的 :探讨大强度训练对大鼠心脏局部肾素 -血管紧张素系统 (RAS)超微结构和功能变化的影响。方法 :以Wistar大鼠为对象 ,进行 8天的大运动量游泳训练 ,观察了大鼠心肌超微结构、心肌收缩功能以及循环和心脏局部的血管紧张素Ⅱ (AⅡ )和血管紧张素转换酶 (ACE)的变化。结果 :大强度训练对大鼠心脏的超微结构、收缩功能产生一定的损害作用 ,功能的改变与超微结构的变化一致 ;在大强度训练状态下 ,循环和心脏局部RAS异常活跃 ;血管紧张素转换酶抑制剂Cap topril能减轻这种损伤。结果提示RAS异常激活可能是大强度训练时心肌受损的重要机制之一。

Captopril对家兔动脉损伤后内膜增生的影响

在家兔颈总动脉球囊损伤模型上 ,观察卡托普利 (Captopril)对术后 2周血浆内皮素 (ET1 )、血管内膜增殖细胞核抗原 (PCNA)阳性表达率、血管内膜厚度的影响。结果表明 :Captopril能显著降低球囊损伤后家兔血浆 ET1 水平及血管内膜 PCNA阳性表达率 (P <0 .0 1) ;与剥脱对照组相比 ,Captopril组血管内膜厚度及管腔狭窄率明显降低 (P <0 .0 1)。提示 :Captopril能抑制血管损伤后内膜的增生 ,可能是通过降低 ET1 水平及抑制平滑肌细胞增殖实现的 ,为

Captopril心肌保护作用的临床研究

Ｃａｐｔｏｐｒｉｌ作为血管紧张素转换酶抑制剂（ＡＣＥＩ）可抑制超氧化物的释放以达到改善心肌功能，减少再灌注损伤。本文对体外循环心内直视手术病人进行手术前后血液动力学及心肌酶学测定，观察Ｃａｐｔｏｐｒｉｌ的氧自由基清除作用。６０例先天性心脏病室缺合并肺动脉高压患者术前口服Ｃａｐｔｏｐｒｉｌ三个月，剂量为５０ｍｇｂｉｄ。另设２０例为对照组。结果显示与对照组相比服药组能明显增加心输出量（Ｐ＜０．０１）而降低肺动脉压力（Ｐ＜０．０５），使手术后即刻ＰＰ／ＰＳ指标趋于正常，达到改善心肌功能的目标。手术前后酶学测定ＣＰＫ，ＣＰＫ－ＭＢ，ＬＤＨ的变化，服药组各次指标均低于对照组，（Ｐ＜０．０ｌ）。Ｃａｐｔｏｐｒｉｌ可以做为非特异性的氧自由基清除剂预防心肌再灌注损伤。

Captopril对急性心肌梗塞后左心室重构的影响

目的 观察Ｃａｐｔｏｐｒｉｌ 对心肌梗塞大鼠血流动力学和心脏形态学的影响，以探讨左室重构的机制；方法 选用大鼠心肌梗塞模型，分为心肌梗塞组、梗塞给药组和假手术组。梗塞前３ 天开始饲以Ｃａｐｔｏｐｒｉｌ（２ｇ／Ｌ） ；结果 心梗后左室重量指数及左室腔半径分别比假手术组增加１０ ．４ ％ 和２４ ．５ ％ ， 使用Ｃａｐ 后左室腔半径降低１２ ．７ ％ ； 心梗后ＬＶＥＤＰ明显增加，使用Ｃａｐｔｏｐｒｉｌ 后使ＬＶＥＤＰ明显降低，亦使ＭＡＰ、ＬＶＳＰ及±ｄｐ／ｄｔｍａｘ 降低（ Ｐ＜ ０ ．０１） ；结论 心梗后应用Ｃａｐｔｏｐｒｉｌ 可以减轻左室重构，改善心功能。

HPLC Determination of Captopril in Human Plasma with Pre-column Derivation and Solid-phase Extraction and Studies on Its Pharmacokinetic and Relative Bioavailability

A new pre-column derivation HPLC method with solid-phase extraction to determine captopril in human plasma was established. Derivation products were extracted by a solid-phase extraction method after the reagent, p-a-dibromoacetophenone(p-BPB), was added in the plasma samples. The samples were analyzed in a VP-ODS column with UV-detector. The calibration curve of captopril was linear within the range of 5~1000 ngmL-1 with r=0.9987, the recovery of this method was 98.652.04%, within day and between day RSD were no more than 3.4% and 8.4% respectively. To study the pharmacokinetics and the relative bioavailability of captopril tablets, two formulations of captopril tablets were given to 18 healthy male volunteers according to a randomized 2-way cross-over design with a 1-week washout period. The respective AUC0~6 , Cmax and Tmax values of the two formulations were 424.5125.7 and 439.4113.3 mghL-1; 505.9244.6 and 504.8172.2 mgL-1; 0.6620.181 and 0.5280.176 h. Results from statistics analysis showed that there were no significant difference between the AUC0~6 , Cmax and Tmax values of the two formulations, The relative bioavailability of tablets I with respect to II was 96.114.6% from AUC0~6 measurement. Bioequivalance was observed between the two tablets.

Captopril抑制鼠视网膜新生血管形成的实验研究

目的探讨captopril对鼠视网膜新生血管形成的抑制作用。方法将60只7d龄小鼠随机分为对照组(30只)和治疗组(30只),置于体积分数75%高氧环境下饲养5d后回到正常空气环境中饲养,出氧箱后治疗组每天1次玻璃体腔注射captopril(2.7mL.kg-1),对照组注射生理盐水注射液(2.7mL.kg-1),连续5d。2组小鼠均于17d时处死并摘除眼球,采用视网膜铺片、HE染色及免疫组织化学法分别观察视网膜血管的改变、计数视网膜新生血管内皮细胞核数并检测基质金属蛋白酶-2蛋白的表达。结果治疗组与对照组相比视网膜血管分布规则、分支良好、新生血管密度减少,且突破视网膜内界膜的血管内皮细胞核数治疗组为(5.39±1.32)个,对照组为(30.43±0.55)个,治疗组明显少于对照组(P<0.05);治疗组基质金属蛋白酶-2染色较对照组减弱。结论玻璃体腔内注入captopril能够有效抑制高氧诱导下的小鼠视网膜新生血管形成,captopril有望成为防治血管增生性视网膜病变的一种有效方法。

captopril对SHR心肌肥厚、心肌Ang’Ⅱ含量和ACE活性的影响

ｃａｐｔｏｐｒｉｌ对ＳＨＲ心肌肥厚、心肌Ａｎｇ’Ⅱ含量和ＡＣＥ活性的影响浙江医科大学附属第二医院心血管病研究室吕俊升，方璐，马骥实验结果证明，Ｃａｐｔｏｐｒｉｌ不仅抑制ＳＨＲ血浆ＡＣＥ活性和降低Ａｎｇ’Ⅱ含量，同时也抑制局部心肌ＡＣＥ活性和Ａｎｇ’Ⅱ...

The Effects of Captopril and Cicaprost on Changes of Cardiac Membrane Fluidity and Lipid Peroxidation

The main purpose of this study was to investigate the protective actions of captopril and cicaprost on changes of membrane fluidity of cultured neonatal rat myocardial cells exposed to anoxia and sugar deprivation.Lipid peroxidation level estimated by determining the thiobarbituric acid reactive substance(TBARS)content and lactate dehydrogenase(LDH)released in culture medium was also observed in order to examine other membrane-related changes due to anoxia.Membrane fluidity was monitored by measuring changes in the steady state fluorescence anisotropy(r_s)by fluorescence spectroscopy.The r_s value,TBARS level and LDH release were significantly increased after 3 h anoxia.Captopril(180 μmol/L),cicaprost(30 nmol/L)and indomethacin(1μmol/L)did not alter r_s, TBARS level and LDH activity of normal cultured neonatal rat myocardial cells.However,both captopril and cicaprost significantly prevented the increases of r_s,TBARS content and LDH release in those cells exposed to anoxia and sugar deprivation.lndomethacin abolished the actions of captopril on TBARS production and LDH release,but maintained its membrane fluidity protection.These results indicate that captopril and cicaprost protect membrane fluidity and lipid peroxidation changes in anoxia- injured myocardial cells.The action mechanism of captopril may be due,in part,to stimulation of prostacyclin synthesis and/or release.

Captopril抑制鼠视网膜新生血管的形成(英文)

目的:探讨Captopril对鼠视网膜新生血管形成的抑制作用。方法:将60只7d龄小鼠随机分为对照组(30只)和治疗组(30只),置于体积分数750±50mL/L高氧环境下饲养5d后回到正常空气环境中饲养,出氧箱后治疗组每天1次玻璃体腔内注射2.7mL/kg Captopril,对照组注射9g/L的氯化钠注射液2.7mL/kg,连续5d。两组小鼠均于17d处死并摘除眼球,采用ADP酶视网膜铺片、HE染色及免疫组织化学法分别观察视网膜血管的改变、计数视网膜新生血管内皮细胞核数及检测MMP-2、PEDF蛋白的表达。结果:治疗组与对照组相比视网膜血管分布规则、分支良好、新生血管密度减少,且突破视网膜内界膜的血管内皮细胞核数目明显减少(P<0.05);治疗组MMP-2染色较对照组减弱,PEDF染色较对照组增强。结论:玻璃体腔内注射2.7mL/kg Captopril能够有效抑制高氧诱导下的小鼠视网膜新生血管形成, Captopril有望成为防治血管增生性视网膜病变的一种有效的方法。

烯丙洛尔脂质体携载Captopril对实验性高血压的治疗作用

烯丙洛尔脂质体携载Ｃａｐｔｏｐｒｉｌ对实验性高血压的治疗作用北京医科大学心血管基础研究所张灵芝，董淑云，唐朝枢我们以前的工作表明烯丙洛尔脂质体主要分布于肺脏和心脏，烯丙洛尔脂质体携载还原型谷胱苷肽（ＧＳＨ）对实验性心肌坏死有明显的疗效（１）。为了进一...

Captopril对肾上腺皮质醇释放的影响

观察血管紧张素转换梅Ｃａｐｔｏｐｒｉｌ在没有外源性血管紧张素Ⅱ（Ａ－Ⅱ）存在的条件下，对离体孵育的豚鼠和狗的肾上腺皮质醇释放量的影响。实验表明，Ｃａｐｔｏｐｔｉｌ抑制皮质醇的释放量（Ｐ＜０．０５）。结果提示：肾上腺内可能有肾素血管紧张素系统（ＲＡＳ）存在，并且通过自分泌或旁分泌的方式调节肾上腺皮质醇的分泌。

Sensitive Voltammetric Determination of Captopril Using a Carbon Paste Electrode Modified with Nano-TiO_2/Ferrocene Carboxylic Acid

A carbon paste electrode (CPE) modified with ferrocene carboxylic acid (FcCA) and TiO2 nanoparticles was constructed by incorporating TiO2 nanoparticles and ferrocene carboxylic acid into the carbon paste matrix. The electrochemical behavior of captopril (CAP) at the surface of the modified electrode was investigated using electroanalytical methods. The modified electrode showed excellent electrocatalytic activity for the oxidation of CAP in aqueous solutions at physiological pH values. Cyclic voltammetric curves showed that the oxidation of CAP at the surface of the modified electrode reduced its overpotential by more than 290 mV. The modified electrode was used for detecting captopril using cyclic voltammetry and square wave voltammetry techniques. A calibration curve in the range of 0.03 to 2400 μmol/L was obtained that had a detection limit of 0.0096 μmol/L (3?) under the optimized conditions. The modified electrode was successfully used for the determination of captopril in pharmaceutical and biological samples.

Simultaneous determination of captopril and hydrochlorothiazide by time-resolved chemiluminescence with artificial neural network calibration

The combined use of chemometrics and chemiluminescence（CL）measurements,with the aid of the stopped-flow mixing technique,developed a simple time-resolved CL method for the simultaneous determination of captopril（CPL）and hydrochlorothiazide（HCT）.The stopped-flow technique in a continuous-flow system was employed in this work in order to emphasize the kinetic differences between the two analytes in cerium（IV）-rhodamine 6G CL system.After the flow was stopped,an initial rise of CL signal was observed for HCT standards,while a direct decay of CL signal was obtained for CPL standards.The mixed CL signal was monitored and recorded on the whole process of continuous-flow/stopped-flow,and the obtained data were processed by the chemometric approach of artificial neural network.The relative prediction error（RPE）of CPL and HCT was 5.9% and 8.7%,respectively.The recoveries of CPL and HCT in tablets were found to fall in the range between 95% and 106%.The proposed method was successfully applied to the simultaneous determination of CPL and HCT in a compound pharmaceutical formulation.

Application of potassium ferricyanide in the spectrophotometric determination of captopril

A novel method for the determination of captopril by spectrophotometer is described in this paper. The experiment is based on the fact that Fe（Ⅲ） is reduced to Fe（Ⅱ） by captopril, then the in sire formed Fe（Ⅱ） reacts with potassium ferricyanide to give the soluble prussian blue at pH 4.00, and its maximal adsorption wavelength （λmax） is 735 nm. Good linear relationship is obtained between the absorbance and the concentration of captopril in the wide range of 0.05-20 μg/mL. The linear regression equation is A = -0.04314 ＋ 0.11423C （μg/mL） with a correlation coefficient R = 0.9998. The detection limit （3σ/k） is 0.04 μg/mL, the molar absorption coefficient is 2.5×10^4 L/mol cm. By mensurating the absorbance of soluble prussian blue, the indirect determination of captopril can be obtained. This method has been successfully applied to determination of captopril in pharmaceutical samples. Analytical results obtained are satisfactory.

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(P<0.05),while TNF- α level in serum of Group Ⅱ was significantly lower in Group Ⅰ(P<0.05).PaCO_2 level was significantly higher(P<0.05),while PaO_2 was significantly lower(P<0.05) in Group Ⅰ and Ⅱ rats than those in Group Ⅲ.PaCO_2 was significantly lower(P<0.05) and PaO_2 was significantly higher(P<0.05) 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.

Determination of captopril in patient human urine using ferrocenemonocarboxylic acid modified carbon nanotubes paste electrode

In this work,we describe a new strategy for the electrochemical determination of captopril（CA） using ferrocenemonocarboxylic acid as a mediator and multiwall carbon nanotubes as sensors in aqueous solution at pH 7.0.The diffusion coefficient（D）,and the kinetic parameters such as electron transfer coefficient（α）.and heterogeneous rate constant（kh）,for CA were also determined using electrochemical approaches.Under the optimized conditions,the electrocatalytic oxidation peak current of captopril showed two linear dynamic ranges with a detection limit of 0.3×10^-6 mol L^-1 captopril.The linear calibration range was 0.8×10^（-6） to 65×10^-6 mol L^-1 using cyclic voltammetry.Finally,this modified electrode was also examined as a selective,simple and precise new electrochemical sensor for the determination of captopril in real samples such as drug and patient human urine.

Preparation and in vitro Release Performance of Sustained-release Captopril/Chitosan-gelatin Net-polymer Microspheres

The captopril/Chitosan-gelatin net-polymer microspheres(CTP/CGNPMs) were prepared using Chitosan(CTS) and gelatin(GT) by the methods of emulsification,cross-linked reagent alone or in combination and microcrystalline cellulose(MCC) added in the process of preparation of microspheres,which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril(CTP). The results indicated that CTP/CGNPMs had a spherical shape,smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio(EMR) and composition of cross linking reagents. Among these factors,the EMR(1/4),CLR(FA+SPP) and 0.75% microcrystalline cellulose(MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER,DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%,9.95±0.77% and 261±42%,respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.