Ramipril在大鼠小肠内转运机制的研究(英文)

Ramipril是长效ACE(血管紧张素转换酶)抑制剂,它与captopril及enalapril药效学性质相似。文章使用了Ussing Chamber体系对Ramipril的小肠转运机制进行了研究。同时研究了头孢菌素(CFX)和乙酰水扬酸(ASA)对Ramipril小肠吸收的影响。CFX为β-内酰胺类抗菌素,研究已证实其和ACE抑制剂在小肠的转运载体相同。临床实验证明ASA影响ACE抑制剂的药代动力学性质。文章结果表明:Ramipril和captopril等ACE抑制剂的肠转运机制有所不同,没有明显的主动转运特点。CFX不抑制ramipril的肠转运。ASA对ramipril的肠转运也没有明显的影响。但是,ramipril确能抑制CFX的肠转运。所以Ramipril可能为一个被动吸收的ACE抑制剂,并不依靠小肠的肽载体进行转运。

Ramipril的心血管作用

Ｒａｍｉｐｒｉｌ是新一代非巯基类血管紧张素转化酶抑制剂，具有药效强、作用时间长、毒副作用少等特点，是治疗各种高血压、充血性心力衰竭和肾功不全等的新的理想药物。本文通过对Ｒａｍｉｐｒｉｌ药代动力学，Ｒａｍｉｐｒｉｌ的心血管作用及抗高血压效果的论述，比较系统的介绍了Ｒａｍｉｐｒｉｌ的药理学和在心血管疾病临床应用的进展。

Ramipril对顺铂和肾缺血再灌所致大鼠肾损害的保护

顺铂ｉｐ或体外直接与肾薄片孵育，均可导致大鼠肾皮质中ＡＴＰ浓度降低，对氨基马尿酸蓄积减少，丙二醛和血尿素氮升高。大鼠肾动脉结扎１ｈ，放开灌流３ｈ，诱发了类似的肾损害。血管紧张素转化酶抑制剂ＲａｍｉＰｒｉｌｉＰ给予接受顺铂处理或接受肾动脉结扎的大鼠，或加入到含顺铂的孵育液中，均能明显抑制顺铂和肾缺血再灌注诱发的ＡＴＰ减少，血尿素氮和丙二醛升高，但对对氨基马尿酸蓄积的减少无保护作用。ＲａｍｉＰｒｉｌ对上述肾损害的保护作用机制可能与其抗脂质过氧化作用有关。

Effects of ramipril on ventricular arrhythmia after myocardial infarction in rabbits

BACKGROUND: V entricular arrhythmia(VA) is one of the most common complications of myocardial infarction(MI), and ventricular tachycardia and fi brillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits.METHODS: Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups: sham-operated(SHAM) group(n=8), MI group(n=8) and MI with ramipril(RAM) group(n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confi rmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril(1 mg/kg per day) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fi brillation(VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student's t test and ANOVA were used for statistical analysis.RESULTS: VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks(2.6±0.8 vs. 12.4±2.9, P<0.05). Twelve weeks after MI, the duration of repolarization for 90%(APD90) of three-tier ventricular myocytes in the MI group was longer than that before MI(258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7, P<0.05). However, the APD90 was not signif icantly different at 12 weeks before and after MI in the RAM group(P>0.05). Moreover, the transmural dispersion of repolarization(TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups(36.2±10.2 vs. 18.7±6.2, 24.9±8.7, P<0.05). But the TDR was not signifi cantly different between the RAM and SHAM groups(18.7±6.2 vs. 24.9±8.7, P>0.05).CONCLUSION: Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.

Development and validation of an RP-HPLC method for simultaneous determination of Ramipril and Amlodipine in tablets

AnRP-HPLC method for the simultaneous determination ofRamipril （RP） andAmlodipine （AL） in tablets was developed and validated by Chinese Pharmacopoeia 2010. The linearity of the proposed method was investigated in the range of 0.01-0.25 mg/mL （r^2=0.9998） for RP and 0.014-0.36 mg/mL （r^2=0.9997） for AL. The limits of detection （LOD） were 0.06 lag/mL and 0.02 μg/mL for RP and AL, and the limits of quantitation （LOQ） were 0.2 Dg/mL and 0.07 μg/mL, respectively. Some major impurities and degradation products did not disturb the detection of RP and AL and the assay can thus be considered stability-indicating.

Effect of ramipril on progression of nonculprit lesions in patients with ST-elevation myocardial infarction after primary percutaneous coronary intervention

Objective To investigate the effect of ramipril on progression of nonculprit lesions in patients with ST-elevation myocardial infarction(STEMI) after primary percutaneous coronary intervention(PPCI). Methods A total of 200 patients(60.1 ± 11.3 years) with STEMI who underwent successful PPCI from January 2010 to December 2013 were enrolled in this study. All patients underwent PPCI as treatment for culprit lesions. Patients were divided into two groups according to the dosage of ramipril used at hospital discharge as follows: high dosage group(2.5–10 mg, q.d.) and low dosage group(1.25–2.5 mg, q.d.). Clinical and angiographic follow-up was performed for 12 months. The primary endpoint was clinically-driven percutaneous coronary intervention(PCI) for nonculprit lesions. The clinical and angiographic features were analyzed. Results Clinical and angiographic follow-up was performed with 87 patients in the high dosage group and 113 patients in the low dosage group. The numbers of patients who underwent additional PCI were six and 20 in the high and low dosage groups, respectively. The rate of having additional PCI performed was lower in the high dosage group than in the low dosage group(6.90% vs. 17.70%, P = 0.03). Conclusions A high dosage of ramipril may prevent progression of nonculprit lesions, which could be the major cause of recurrent PCI in patients with STEMI after PPCI.

Stress Degradation Behavior of a Polypill and Development of Stability Indicating UHPLC Method for the Simultaneous Estimation of Aspirin, Atorvastatin, Ramipril and Metoprolol Succinate

A novel, sensitive and precise UHPLC method has been developed and validated for the simultaneous determination of the all the active components of a Polypill viz Zycad, i.e., Aspirin (ASP) Atorvastatin (ATV), Ramipril (RMP) and Metoprolol (MTP) in Zycad tablet dosage form in the presence of degradation products. Forced degradation of individual as well as combination of all the drug substances components of Polypill was conducted in accordance with ICH guidelines. Acidic, basic, neutral, and oxidative hydrolysis, thermal stress, and photolytic degradation were used to assess the stability-indicating power of the method. Use of 100 × 2.1 mm, 1.7 μm stationary phases with simple mobile phase combination buffer consisting of 0.1% Perchloric acid (adjusted to pH 2.5) and Acetonitrile, delivered in a gradient mode and quantitation was carried out using ultraviolet detection at 215 nm with a flow rate of 0.6 mL?min–1. The method was optimized using samples generated by forced degradation studies. The method was validated for linearity, accuracy (recovery), precision, Specificity and robustness. The method was linear in the range of 37.5 to 150.0 μg?mL–1 for ASP, 5.0 to 20.0 μg?mL–1 for ATV and 2.5 to 10.0 μg?mL–1 for RMP and 25.0 to 100.0 μg?mL–1 for MTP.

<i>Low Dose</i>Irbesartan Has a Renoprotective Effect as High Dose Ramipril in Diabetic Rats Treated with Insulin

Objectives: The aim of this study is to compare the efficacy of the anti-angiotensinic drug, ramipril and irbesartan on the vascular protection of kidneys of streptozotocin (STZ)-induced diabetic rats (DR). Methods: 110 male albino rats were divided into 7 main groups. Group-1 (10 normal control rats;NC). Group-2 (10 rats) was injected intra-peritoneally with STZ (Diabetic Rats;DR). Group-3 (10 DR) is controlled by insulin. Groups 4 to 7 (20 DR), each is subdivided into two subgroups that received either low or high dose of ramipril or irbesartan with or without insulin. Two months post treatment, rat-tail blood was collected to measure: Fasting blood sugar, HbA1c, total serum proteins, albumin and lipid profiles. Urine was collected to measure albuminuria. Kidneys were isolated for histopathological study. Results: Biochemically, both ramipril and irbesartan (without insulin) lowered albumin concentration in urine samples especially at high doses. Histopathologically, there is no beneficial response of both drugs without insulin. Combination of insulin together with either drug has beneficial effects biochemically and histopathologically at high doses. Low dose irbesartan only has renoprotective effect in DR treated with insulin. The other biochemical parameters showed negligible response to both drugs. Conclusion: Low dose irbesartan and high doses of both drugs have renoprotective effect in DR treated with insulin.

Effect of Ramipril on Renin-Angiotensin-Aldosterone System of Young and Middle-Aged Patients with Hypertension

Objective:To explore the effect of Ramipril on renin-angiotensin-aldosterone system of young and middle-aged patients with hypertension.Methods 90 young and middle-aged patients with hypertension who had been seeking treatment in the hospital between August 2017 and August 2018 were selected and randomly divided into a control group and an observation group according to the random number table,with 45 cases in each group.The control group received Amlodipine for treatment,whereas the observation group was given Amlodipine combined with Ramipril for treatment.The hemodynamic indexes,blood lipid,blood pressure,angiotensinⅡ(AngⅡ),plasma renin(PRA),aldosterone(ALD)levels and incidence of adverse reactions during the medication in the two groups were compared before and after treatment.Results After treatment,thefibrinogen,plasma viscosity and whole blood viscosity in the observation group were significantly higher than those in the control group,with statistically significant difference between the two groups(P<0.05);total cholesterol(TC),triacylglycerol(TG)and low density lipoprotein cholesterin(LDL-C)in the observation group were significantly lower than those in the control group,and statistically significant difference was registered between the two groups(P<0.05);the diastolic pressure and systolic pressure in the observation group were decreased more significantly compared with the control group,with statistically significant difference shown between the two groups(P<0.05);the AngⅡ,ALD and PRA levels in the observation group were significantly lower than the control group,and the difference between two groups were statistically significant(P<0.05);during the medication,no significant bleeding or liver and kidney function damages occurred in the two groups.Conclusions For young and middle-aged patients with hypertension,the treatment with Ramipril,which is of high safety,can effectively improve the activity of their renin-angiotensin-aldosterone system,reduce the level of blood pressure and AngⅡ,ALD and PRA levels.

Ramipril的血流动力学作用及其作用机制

目的：明确ｒａｍｉｐｒｉｌ治疗心力衰竭的效应及其作用机制。方法：１２名重度心力衰竭患者口服ｒａｍｉｐｒｉｌ５ｍｇ，观察服药后２４ｈ血流动力学变化。放免法测定服药前后血浆肾素活力（ＰＲＡ）和血管紧张素Ⅱ（ＡｎｇⅡ）浓度，紫外法测定血管紧张素转化酶（ＡＣＥ）活力的变化。结果：服药后２ｈ即可见有明显的血流动力学改善，最大效应出现在服药后４ｈ，一次服药作用可维持２４ｈ。Ｒａｍｉｐｒｉｌ使ＡＣＥ活力和ＡｎｇⅡ浓度明显而持久地降低，ＰＲＡ反应性增高。结论：Ｒａｍｉｐｒｉｌ是一种作用强大的长效ＡＣＥ抑制剂，可望成为治疗严重心力衰竭的安全有效药物。

Effect of aliskiren on arterial stiffness, compared with ramipril in patients with mild to moderate essential hypertension

Background Aliskiren is a novel blood pressure-lowering agent acting as an oral direct renin inhibitor. The aim of this study was to assess the effect of aliskiren on arterial stiffness, compared with that of ramipril in mild to moderate essential hypertensive patients. Methods Following a two week placebo run-in period, patients with a mean sitting diastolic blood pressure （ms-DBP） 〉95 and 〈110 mmHg （1 mmHg=0.133 kPa）, and a mean sitting systolic blood pressure （ms-SBP） 〈180 mmHg were randomly allocated to treatment with aliskiren （150 mg/d, n=20） or ramipril （5 mg/d, n=20） for eight weeks. Blood pressure, plasma renin activity, and the brachial-ankle pulse wave velocity （ba-PWV） were measured before and after eight weeks of treatment. Results Eight weeks of treatment significantly decreased systolic blood pressure and diastolic blood pressure in both the aliskiren group and ramipril group. The hypotensJve effect did not differ between the two groups. Plasma renin activity decreased after aliskiren treatment and increased after ramipril treatment. There was no significant difference in baseline ba-PWV between the aliskiren and ramipril groups （P=-0.892）. The ba-PWV was significantly reduced in both the aliskiren group （1535 （1405-1666） vs. 1464 （1360-1506） cm/s） （P 〈0.01） and the ramipril group （1544 （1433-1673） vs. 1447 （1327-1549） cm/s） （P 〈0.01）. No statistically significant difference was found in the decline of ba-PWV between the two groups （P=0.766）. Conclusions The current study revealed that aliskiren （150 mg/d） could ameliorate arterial stiffness and its effect was similar to ramipril （5 mg/d） in mild to moderate hypertensive patients, indicating that in addition to lowering blood pressure, aliskiren had beneficial effect on vascular protection.

Telmisartan, ramipril, or both in high-risk Chinese patients： analysis of ONTARGET China data

Background The results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial （ONTARGET） indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China. Methods A total of 1159 high-risk patients were randomized into three treatment groups： with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years. Results The mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population （47.7% vs 20.9%）. In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population （8.5% vs. 4.5%）. Greater systolic blood pressure reduction （-9.8 mmHg）, and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group （2.6% vs. 1.6% and 1.0%）. Conclusions There was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome, particularly safety. Compliance with study medications was good. The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China.

Benefits of Fixed Dose Combination of Ramipril/Amlodipine in Hypertensive Diabetic Patients： A Subgroup Analysis of RAMONA Trial

Background： Combination of angiotensin-converting enzyme inhibitors and calcium channel blockers has been successfully used in the ant±hypertensive therapy for many years. Fixed dose combinations of ramipril/amlodipine have a benefit effect for patients to achieve target blood pressure （BP）. This study aimed to assess the efficacy and safety of fixed dose combinations oframipril and amlodipine （Egiramlon） in hypertensive diabetic patients. Methods： Hypertensive diabetic patients who were enrolled into the RAMONA trial were included in this open, prospective, Phase Ⅳ observational clinical study. Patients had mild-to-moderate hypertension and failed to reach target BP levels through their previous therapy. During the four months of observation, patients took part in three visits （1 st day - visit 1, 1 st month = visit 2, and 4th month = visit 3） where they received a fixed dose combination of 5/5, 5/10, 10/5, or 10/10 nag ramipril/amlodipine, respectively, with the possibly required dose titrations, based on the decision of their attending physician. Target BP for diabetic patients was 〈 140/85 mmHg. BP levels were measured in all visits, by taking two readings at 2-min interval. Laboratory tests including full blood count, renal function test, electrolytes, blood glucose, serum cholesterol, uric acid, triglycerides, liver function test, creatinine kinase, and midstream urinalysis were performed at visit 1 and visit 3. Results： The 6423 patients completed the study. Among these patients, 1276 （19.9%） patients suffered from type 2 diabetes mellitus. The mean age of these diabetic patients was 64.2 ±10.0 years; 707 （55.4%） patients were males. Target BP was achieved by 891 （69.8%） of diabetic patients at visit 3 （primary endpoint）. BP decreased from 157.5/91.3 ±9.6/7.6 mmHg （visit 1） to 130.9/79.6 ± 7.4/5.8 mmHg （visit 3）. As for the secondary endpoint of the study, total cholesterol decreased from 5.50 ±1.13 mmol/L （visit 1 ） to 5.20 ±0.95 mmol/L （P = 0.000）, low-density lipoprotein cholesterol decreased from 3.20 ±0.93 mmol/L to 3.00 ±0.77 mmol/L （P = 0.000）, triglyceride decreased from 2.20 ±1.14 mmol/L to 2.00 ±1.97 mmol/L （P = 0.000）, while high-density lipoprotein cholesterol increased from 1.30 ±0.42 to 1.35 ±0.30 mmol/L （P = 0.001） until the end of the 4th month （visit 3）. Fasting blood glucose of the hypertensive diabetic patients decreased from 7.20 ± 1,88 mmol/L to 6.70 ± 1.38 mmol/L （P = 0.000）, while HbAlc decreased from 7.90 ± 1.78% to 7.60 ± 1.83% （P = 0.000）. Various fixed dose combinations of ramipril/amlodipine were well tolerated and no adverse event related to the use of the medicine has appeared. Conclusions： The fixed dose combination of ramipril/amlodipine was effective in hypertensive diabetic patients who failed to reach target BP previously.

雷米普利联合卡维地洛治疗心衰合并心律失常的效果及对血清cTnI、NT-pro BNP水平的影响研究

目的探讨雷米普利联合卡维地洛治疗心力衰竭合并心律失常的效果及对血清肌钙蛋白I(Troponin I,cTnI)、N-端前体脑钠肽(N-terminal Pro-B-type Natriuretic Peptide,NT-pro BNP)水平的影响研究。方法选取2021年6月—2023年6月肥西县中医院收治的心力衰竭合并心律失常80例患者,按照随机数表法分为研究组与对照组,各40例。对照组采用雷米普利治疗,研究组采用雷米普利联合卡维地洛治疗。对比两组的临床疗效及血清cTnI、NT-pro BNP水平。结果研究组总有效率(95.00%)高于对照组总有效率(70.00%),差异有统计学意义(χ^(2)=8.658,P<0.05);治疗后,研究组的血清cTnI、NT-pro BNP水平均低于对照组,差异有统计学意义(P均<0.05)。结论心力衰竭合并心律失常患者应用雷米普利联合卡维地洛进行治疗,能有效降低血清cTnI、NT-pro BNP水平,治疗效果显著。

急性心肌硬死后Ramipril或安慰剂治疗心力衰竭随访研究

据《The Lancet》1997年349卷第9064期报道 1989～1992年在英国进行的急性心肌梗死Ramipril疗效(AIRE)的研究中,关于血管紧张素转换酶(ACE)抑制剂对急性心肌梗死(AMI)

沙库巴曲缬沙坦钠与雷米普利治疗老年急性失代偿心力衰竭合并肺动脉高压患者的效果比较

目的:比较沙库巴曲缬沙坦钠与雷米普利治疗老年急性失代偿心力衰竭(ADHF)合并肺动脉高压(PAH)的效果。方法:选取2020年11月—2022年11月于福建医科大学附属泉州第一医院就诊的100例ADHF合并PAH老年患者作为研究对象,按照随机数表法将患者分为对照组和观察组,各50例。对照组予以雷米普利治疗,观察组予以沙库巴曲缬沙坦钠治疗。比较两组治疗效果、治疗前后血清指标和心功能指标、不良反应发生情况。结果:治疗3个月后,观察组总有效率高于对照组,差异有统计学意义(P<0.05)。治疗3个月后,两组N末端B型利钠肽原(NT-proBNP)、转化生长因子β_(1)(TGF-β_(1))水平较治疗前降低,6分钟步行试验(6MWT)、心排血量及左心室射血分数(LVEF)水平较治疗前升高,且观察组优于对照组,差异有统计学意义(P<0.05)。观察组治疗期间不良反应发生率低于对照组,差异有统计学意义(P<0.05)。结论:沙库巴曲缬沙坦钠治疗老年ADHF合并PAH较雷米普利的临床效果显著,可明显提升心脏功能,改善血清相关指标,且安全性良好。

沙库巴曲缬沙坦对比雷米普利对接受PCI治疗的AMI患者早期心室重构的影响:一项单中心倾向性匹配分析

目的:通过倾向性评分匹配法探讨沙库巴曲缬沙坦(Sacubitril/Valsartan,LCZ696)与雷米普利相比对急性心肌梗死(AMI)经皮冠状动脉治疗患者早期左室重构的影响。方法:回顾性收集2019年12月1日—2021年8月就诊泰达国际心血管病医院行经皮冠状动脉治疗的195例急性心肌梗死患者病例资料,根据出院用药分为沙库巴曲缬沙坦组(94例)和雷米普利组(101例),通过倾向性评分匹配减少药物选择偏差和混杂因素,比较两组治疗1月后心脏超声指标[左室舒张末直径(LVDd)、室间隔厚度(IVS)、左室后壁(LVPW)、左心室舒张末期容积(LVEDV)、左心室收缩末期容积(LVESV)、每搏量(SV)、左室射血分数(LVEF)]的变化。结果:匹配后,沙库巴曲缬沙坦组和雷米普利组各66例。治疗1个月后两组LVEDV[102.00(88.75,113.25)mL vs.94.00(82.75,110.50)mL,Z=-1.179,P=0.238]、LVESV[39.50(31.75,52.00)mL vs.37.00(29.75,46.00)mL,Z=-1.639,P=0.101]和LVEF[(58.77±7.66)%vs.(60.50±6.77)%,t=-1.373,P=0.172]差异均无统计学意义。两组LVEF均较治疗前升高,沙库巴曲缬沙坦组[58.00(49.00,62.25)%vs.59.00(53.75,64.25)%,Z=-3.460,P=0.001],雷米普利组[57.50(51.75,63.50)%vs.60.00(56.00,66.00)%,Z=-3.167,P=0.002]差异有统计学意义。结论:应用沙库巴曲缬沙坦和雷米普利治疗1个月后,两组患者LVEF均较治疗前改善。但在逆转心肌梗死后早期左室重构并未发现沙库巴曲缬沙坦优于雷米普利。

雷米普利对糖尿病大鼠心肌缺血/再灌注损伤的保护作用

目的研究雷米普利(RAM)对糖尿病大鼠心肌缺血/再灌注损伤的保护作用。方法链脲佐菌素致糖尿病大鼠被随机分为缺血/再灌注(I/R)、缺血预适应(IPC)和RAM3组。RAM组每天用RAM(1mg·kg-1)灌胃,IPC和I/R组用等体积生理盐水灌胃。4wk后各组动物均经历心肌缺血/再灌注损伤,IPC组于缺血前行心肌缺血预适应。连续监测心电图,检测心肌梗死范围、心肌细胞凋亡、凋亡蛋白Bcl-2与Bax表达,光镜下观察心肌形态学改变。结果与I/R组比较,RAM及IPC组ST-段抬高幅度降低,室早出现时间推迟,持续时间缩短,室速、室颤发生率降低,心肌梗死范围缩小,心肌细胞凋亡减轻,Bcl-2/Bax比值升高。结论连续4wk应用RAM可减轻糖尿病大鼠心肌缺血/再灌注损伤。

曲美他嗪与雷米普利对心力衰竭大鼠心肌细胞凋亡及半胱氨酸天冬氨酸蛋白酶3的影响

目的探讨曲美他嗪与雷米普利单用及联合应用对慢性心力衰竭大鼠左心室心肌细胞凋亡情况以及半胱氨酸天冬氨酸蛋白酶3(Caspase-3)表达水平的影响。方法雄性Wistar大鼠50只随机分为假手术组、模型组、曲美他嗪组、雷米普利组和联合用药组(曲美他嗪+雷米普利),每组10只。采用肾上腹主动脉缩窄法制作慢性心力衰竭模型,观察各组左心室舒张末压、左心室压力最大上升及下降速率(±dp/dtmax);TUNEL法检测心肌细胞凋亡指数;SP免疫组织化学法检测各组大鼠左心室心肌Caspase-3水平的表达,RT-PCR测定Caspase-3mRNA水平。结果与模型组比较,曲美他嗪组、雷米普利组和联合用药组左心室舒张末压、心肌凋亡指数明显降低,±dp/dtmax明显升高,差异有统计学意义(P<0.01),Caspase-3蛋白及mRNA表达水平明显降低,差异有统计学意义[(0.14±0.01、0.14±0.02和0.08±0.02)vs(0.22±0.02),(0.54±0.02、0.54±0.02和0.32±0.02)vs(0.91±0.02),P<0.01]。结论曲美他嗪与雷米普利单用及联合应用均可有效改善心功能、抑制心肌细胞凋亡,联合用药的疗效优于单独用药。