缬沙坦对家兔梗死心肌MDA、SOD、ATPase活性的影响

目的：探讨缬沙坦（Valsartan,VAL）对心肌梗死（MI）作用及其作用机制。方法：结扎冠状动脉左前降支建立心肌梗死建模,随即分为假手术组、心肌梗死组、VAL组。然后分别在各组中应用BL-420F生物机能实验系统测定右颈总动脉插入动脉导管的心肌梗死（MI）的左室收缩压（LVSP）、左室舒张末压（LVEDP）;分别采用黄嘌呤氧化法和硫代巴比妥酸显色法测定心肌丙二醛（MDA）和超氧化物歧化酶（SOD）含量以及应用定磷法心肌细胞细胞膜Na＋-K＋-ATPase、Ca2＋-ATPase活性。结果：VAL可降低MI家兔的收缩压不明显（P〉0.05）,但降低舒张末降低明显（P〈0.01）;VAL使MI家兔增高的MAD显著降低（P〈0.01）;使MI家兔降低的SOD值显著恢复、增加（P〈0.01）;VAL可使MI家兔降低的Na＋-K＋-ATPase和Ca2＋-ATPase活性恢复、增加（P〈0.05）。结论：VAL可能通过稳定细胞膜抗脂质过氧化反应及提高清除氧自由基以及促进MI后心肌细胞膜Na＋-K＋-ATPase ATPase和Ca2＋-AT-Pase活性的途径改善心肌梗死（MI）作用。     

Cancer risk associated with the use of valsartan in Korea: A nationwide cohort study

BackgroundDespite valsartan’s widespread use, few studies have explored its potential carcinogenicity. We evaluated the association between valsartan and cancer.MethodsWe conducted a retrospective cohort study using data from 2002 to 2015 gathered from the National Health Insurance database. Patients with hypertension aged ≥ 30 who used valsartan or other angiotensin II receptor blockers (ARBs) were included. Eligible patients were those with no prior history of the use of any ARBs, diagnosis of cancer, or organ transplantation in the 4 years predating their first use of the drugs of interest. The primary and secondary outcomes included the occurrence of all cancers and site-specific solid cancers, respectively. After applying propensity score (PS) matching, Cox regression was used to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs).ResultsA total of 1,550,734 individuals were identified as new users of valsartan or other ARBs. Of the 153,047 valsartan users, 16,047 were diagnosed with cancer. No increased risk of overall cancer was observed in valsartan users as compared to other ARB users (aHR = 1.00; 95 % CI, 0.98–1.02). Valsartan was, however, associated with a slightly elevated risk of liver (aHR = 1.09; 95 % CI, 1.01–1.16) and kidney cancer (aHR = 1.11; 95 % CI, 1.02–1.22).ConclusionCompared with other ARBs, valsartan did not increase the risk of overall cancer. A slightly increased risk for some solid cancers was associated with valsartan use, though the absolute rate difference was small.     

缬沙坦胶囊联合肾炎康复片治疗糖尿病微量蛋白尿的研究

目的：研究缬沙坦联合肾炎康复片治疗糖尿病微量蛋白尿的疗效及安全性。方法：采用随机、对照原则将60例有微量蛋白尿期糖尿病患者分为缬沙坦对照组（A组）和缬沙坦联合肾炎康复片治疗组（B组）,每组各30例。A组给予缬沙坦160mg,每日1次口服;B组给予肾炎康复片（薄膜衣片）每次5粒,每日3次口服和缬沙坦160mg,每日1次口服。疗程均为12w。比较2组治疗前、治疗第4、8和12w尿白蛋白排泄率（UAER）及治疗前、后肾功能、24h尿蛋白定量等生化指标的变化及肌酐50％倍增率。结果：2组治疗后血压、Scr、CRP指标均低于治疗前（P〈0．05）,而血FBG、PBG、HbAlc、Alb、BUN、24h尿蛋白定量指标变化无差异（P〉0．05）;B组治疗后与对照组比较,B组有较低Scr、CRP值（P〈0．05）,而余生化指标及血压变化无差异（P〉0．05）,B组第8、12w时尿蛋白排泄率下降幅度低于A组（P〈0．05）,B组治疗中12w的肌酐50％倍增率低于A组（P〈0．05）。结论：缬沙坦胶囊联合肾炎康复片治疗糖尿病微量蛋白尿是有效安全的。     

缬沙坦对维持性血液透析患者心脏功能和结构的影响

目的:探讨缬沙坦对维持性血液透析(maintenance hemodialysis,MHD)患者心脏功能和结构的影响。方法:100例MHD患者,随机分为治疗组(50例)与对照组(50例),对照组仅予基础治疗,治疗组加予口服缬沙坦治疗,总疗程为6个月。观察治疗前后超声心动图指标变化。结果:与治疗前及对照组同期比较,治疗组心脏结构指标左房收缩末期内径(LAD)、左室舒张末期内径(LVDD)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)、左房内径指数(LAI)、左室重量指数(LVMI)及相对室壁厚度(RWT)有所降低,心脏功能指标:左室射血分数(LVEF),左室短轴缩短率(FS),二尖瓣口舒张早期和晚期最大血流速度比(E/A)值有所提高,差异均有统计学意义(P<0.05)。对照组超声心动图各项指标与治疗前相比变化不明显(P>0.05)。结论:缬沙坦能延缓或逆转左心室肥厚,明显改善左室舒张功能,有助于改善MHD患者心脏重构,改善心脏功能,从而延缓慢性肾功能衰竭尿毒症期患者的左心室重塑,降低心血管疾病的发生率和死亡率。缬沙坦对MHD患者心血管疾病并发症的预防和治疗及提高MHD患者生存率有一定临床指导意义。     

缬沙坦联合氨氯地平治疗高血压伴左心肥厚的疗效及对心功能的影响

目的:通过探讨缬沙坦联合氨氯地平治疗高血压伴左心肥厚患者的疗效及对心功能的影响,为临床治疗提供依据。方法:选择2010年1月~2014年12月我院收治的高血压伴左心室肥厚患者共120例,按照随机数字表法随机分为观察组和对照组。对照组患者给予氨氯地平,观察组患者缬沙坦联合氨氯地平治疗,治疗6个月后,观察两组患者舒张压(DBP)、收缩压(SBP)、心率(HR)、室间隔厚度(IVST),左室后壁厚度(LVPWT)、左室舒张末期内径(LVDd)和左室重量指数(LVMI)。结果:治疗后,两组患者SBP、DBP和HR均较治疗前显著降低,差异有统计学意义(P0.05);观察组患者SBP、DBP和HR均低于对照组,差异有统计学意义(P0.05)。治疗后,两组患者IVST、IVPWT、LVDd和LVMI均较治疗前显著降低,差异有统计学意义(P0.05);观察组患者IVST、IVPWT、LVDd和LVMI均低于对照组,差异有统计学意义(P0.05)。结论:缬沙坦联合氨氯地平治疗高血压伴左心肥厚患者,能够降低患者血压、逆转左心室肥厚,改善患者心功能,疗效优于氨氯地平单独治疗,值得临床推广应用。     

缬沙坦联合苯磺酸左旋氨氯地平治疗201例高危高血压患者的疗效评价

目的探讨缬沙坦联合苯磺酸左旋氨氯地平治疗高危高血压患者的临床疗效。方法选择常州市新北区春江人民医院2014年6月至2016年6月收治的201例高危高血压患者,随机分为治疗组(n=101)和对照组(n=100)。对照组采用苯磺酸左旋氨氯地平治疗,治疗组在对照组的基础上联合缬沙坦治疗。观察比较两组收缩压和舒张压水平、血钾和血肌酐浓度、SF-36评分及不良反应发生情况。结果治疗后,两组收缩压和舒张压水平均显著降低(P0.05),且观察组低于对照组(P0.05);治疗后4周,观察组收缩压和舒张压水平亦均显著低于对照组(P0.05)。治疗后,两组血K+浓度、血肌酐浓度均显著降低(P0.05),且观察组低于对照组(P0.05);治疗后4周,观察组血K+浓度和对照组无差异(P0.05),血肌酐浓度亦低于对照组(P0.05)。两组SF-36评分均显著升高(P0.05),且观察组显著高于对照组(P0.05)。观察组不良反应率为5.94%,对照组为8.00%,两组比较无统计学意义(χ~2=1.612,P=0.880)。结论缬沙坦联合苯磺酸左旋氨氯地平治疗高危高血压临床疗效显著,安全性高,可以有效改善患者生活质量,值得推广应用。     

AT2 receptor mediates the cardioprotective effects of AT1 receptor antagonist in post-myocardial infarction remodeling

There are two subtypes of angiotensin (Ang) II receptors, AT1R and AT2R. It is established that clinical use of specific AT1R blocker (ARB) improves the long-term prognosis of heart failure. However, scientific basis for such effects of ARB is incompletely understood. The present study was designed to determine whether ARB inhibits the left ventricular (LV) remodeling that occurs early after myocardial infarction (MI) and whether the benefit of ARB is mediated by blockade of AT1R itself or by stimulation of AT2R resulting from AT1R blockade. MI was induced in AT2R-knockout mice and wild-type mice. Administration of valsartan, an ARB, or vehicle was started soon after the surgery and continued for two weeks. Infarction caused significant increase in end diastolic and end systolic LV dimensions, LV/body weight ratio, and myocyte cross-sectional area (MCSA) in both strains to a similar extent. Lung/body weight ratio, an index of pulmonary congestion, was also significantly increased in both strains, but the magnitude of increase was significantly larger in knockout mice. Valsartan significantly reduced LV dimensions, LV/body weight ratio, MCSA, and lung/body weight ratio in wild-type mice. In knockout mice, however, valsartan failed to inhibit the increases in LV dimensions and LV/body weight ratio. After the treatment, lung/body weight ratio in the mutant strain was significantly larger than that in the wild-type mice. Valsartan attenuates acute phase post-infarction remodeling and ameliorates heart failure, and a large part of its cardioprotective effect was mediated by AT2R.     

缬沙坦对腹主动脉缩窄大鼠心肌及冠状动脉重塑的影响

目的观察血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)Ⅰ型(AT1)受体拮抗剂缬沙坦对腹主动脉缩窄(AC)大鼠心肌与冠状动脉重塑的影响,并探讨其可能的机制。方法将腹主动脉缩窄术后SD大鼠随机分为:AC对照组;AC 低剂量缬沙坦(1mg/kg/d)组;AC 高剂量缬沙坦(30mg/kg/d)组,每组8只。另设假手术组8只作为正常对照。假手术组及AC对照组给予安慰剂灌胃。治疗6周后,检测各组大鼠颈动脉压、左室重量指数(leftventricularmassindex,LVMI)。vanGieson染色检测心肌胶原容积分数(collagenvolumefraction,CVF)及冠状动脉壁厚度/内径比值。放射免疫法检测血浆及心肌中AngⅡ浓度。免疫组化法检测心脏结缔组织生长因子(connectivetissuegrowthfactor,CT-GF)的表达。结果AC对照组大鼠颈动脉压、LVMI、CVF、冠状动脉中层/内径比值以及CTGF表达均显著高于假手术组(P<0·01)。与AC对照组相比,上述所有指标在高剂量缬沙坦组均明显下降(P<0·01)。低剂量缬沙坦组颈动脉压与AC对照组相比无显著性差异(P>0·05),但上述其他指标则明显低于AC对照组(P<0·05或P<0·01)。结论缬沙坦能有效抑制腹主动脉缩窄大鼠的心肌及冠状动脉重塑。其可能机制是阻滞了心肌局部的AT1受体,并下调CTGF的表达。     

缬沙坦对动脉粥样硬化兔血清IL-8和TNF-α水平的影响

目的：研究缬沙坦对动脉粥样硬化兔血清IL-8和TNF-α水平的影响。方法：将30只实验兔随机分为3组,每组10只,即正常对照组：喂以普通饲料;高脂饮食组：喂以高脂饮食（含15%蛋黄粉,0.5%胆固醇和5%猪油的饲料）6周,后给予10 ml/d生理盐水4周;药物干预组：喂以高脂饮食6周,后给予缬沙坦（10 mg/kg/d）治疗4周。饲养6周和10周时分别经兔耳缘静脉取血,通过酶联免疫法检测各组兔血清中IL-8和TNF-α的水平。结果：饲养第6周时,高脂饮食组和药物干预组兔血清TNF-α和IL-8水平均较正常对照组明显升高,差异均具有统计学意义（P〈0.05）,而高脂饮食组与药物干预组比较差异无统计学意义（P〉0.05）。饲养第10周时,即缬沙坦干预4周后,药物干预组与建模6周时比较,血清TNF-α及IL-8水平均明显下降,差异具有统计学意义（P〈0.05）,且与高脂饮食组比较,血清TNF-α及IL-8水平亦明显下降,差异具有统计学意义（P〈0.05）。结论：动脉粥样硬化时,血清IL-8和TNF-α升高,缬沙坦能明显降低动脉粥样硬化中IL-8和TNF-α水平,从而发挥抗动脉粥样硬化作用。     

硝苯地平缓释片联合缬沙坦治疗原发性高血压疗效和 安全性的Meta 分析

摘要目的：系统评价硝苯地平缓释片联合缬沙坦治疗原发性高血压的疗效和安全性。方法：计算机检索PubMed、Cochrane Library 、CBM、CNKI、VIP 等数据库,按照纳入和排除标准纳入依硝苯地平缓释片联合缬沙坦治疗原发性高血压的随机对照试验 （RCT）,并补充检索纳入研究的参考文献;按Cochrane 系统评价方法由两名评价员独立评价纳入文献质量、提取资料并交叉核对 无误后,采用RevMan 5.1 软件进行统计学分析。结果：共纳入4 个RCT,包括共450例患者,其研究质量均为C级。Meta 分析结 果显示：硝苯地平缓释片联合缬沙坦治疗原发性高血压的显效率[RR=1.29, 95%CI(1.08～1.55), P< 0.01]、总有效率[RR=1.19, 95% CI(1.10～1.29), P<0.01]和无效率[RR=0.38, 95%CI(0.24～0.62), P<0.01]与单用硝苯地平缓释片比较,两组差异有统计学意义,两组 有效率差异无统计学意义[RR=1.02, 95%CI(0.97～1.32), P>0.01]。结论：现有证据表明：硝苯地平缓释片联合缬沙坦治疗原发性高 血压在显效率,总有效率和无效率方面优于硝苯地平缓释片单用,不良反应与苯地平缓释片单用无明显差异,但远期疗效尚不清 楚,尚需更多高质量的随机双盲对照试验证实。