缬沙坦对大鼠心室肌细胞L-型钙通道电流的影响

目的研究AT1受体拮抗剂缬沙坦对正常大鼠心室肌细胞L-钙电流(Ica-L)的影响。方法采用全细胞膜片钳技术,观察0.4μmol/L的缬沙坦引起单个大鼠心室肌细胞L型钙通道电流变化。结果0.4μmol/L缬沙坦使正常大鼠心室肌细胞L型钙电流峰值明显降低(P<0.01),I-V曲线上移,但不改变其激活电位、峰值电位和反转电位。不影响通道稳态激活曲线,使稳态失活曲线左移。结论0.4μmol/L缬沙坦可直接阻断大鼠心室肌细胞L型钙通道,改变心室肌细胞的电生理特性,可能是其抗心律失常的机制之一。     

Sacubitril/Valsartan for heart failure: A protocol for systematic review and meta-analysis

Background:Sacubitril–valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF). However, the effects of sacubitril–valsartan have never been systematically evaluated. Therefore, we performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of sacubitril–valsartan in patients with HF.Methods:We selected 8 databases, including PubMed, the Web of Science, Embase, Cochrane Library, the Chinese National Knowledge Infrastructure, the Chinese Science Journal Database, Wanfang Data, and the Chinese Biomedical Literature Database. The search time was from database establishment to March 2022. Two reviewers will screen the records and include quality studies according to inclusion criteria independently. Two reviewers will assess the risk of bias of the included studies by the “Risk of Bias Assessment Tool” of the Cochrane Handbook for randomized controlled trials. Statistical analysis will be performed with Review Manager software 5.3.Results:A synthesis of current evidence of sacubitril–valsartan for treating HF will be provided in this protocol.Conclusion:The results of this study will provide a theoretical basis for the clinical use of sacubitril–valsartan to treat HF.     

Emerging trends in sacubitril/valsartan research: A bibliometric analysis of the years 1995–2021

Background:Sacubitril/valsartan has been approved for the treatment of heart failure (HF) patients with reduced ejection fraction; since then, it gradually became a new star drug in the therapy of HF. Nevertheless, the effectiveness of sacubitril/valsartan remains under investigation. Thus far, only a few bibliometric studies have systematically analyzed the application of sacubitril/valsartan.Methods:Publications on sacubitril/valsartan were retrieved from the Web of Science Core Collection on April 29, 2021. Data were analyzed using Microsoft Excel 2019 (Redmond, WA), VOS viewer (Redmond, WA), and Cite Space V (Drexel University, Philadelphia, PA).Results:A total of 1309 publications on sacubitril/valsartan published from 1995 to 2021 were retrieved. The number of publications regarding sacubitril/valsartan increased sharply in the last 6 years (2015–2021), and American scholars authored >40% of those publications. Most were published in the European Journal of Heart Failure, the United States was the bellwether with a solid academic reputation in this area. Solomon published the highest number of related articles and was the most frequently cited author. “Heart failure” was the leading research hotspot. The keywords, “inflammation,” “fibrosis,” and “oxidative stress” appeared most recently as research fronts.Conclusions:Research attention should be focused on clinical trial outcomes. Considering its effectiveness in HF, the mechanisms and further applications of sacubitril/valsartan may become research hotspots in the future and should be closely examined.     

苯那普利和缬沙坦联合应用对大鼠阿霉素肾病的影响

目的:探讨苯那普利和缬沙坦对大鼠阿霉素肾病的干预作用。方法:实验Wistar大鼠实行右肾切除手术,以阿霉素尾静脉注射造模,分别用苯那普利、缬沙坦及两者联合灌胃。用药后2～8周检测血、尿标本;透射电镜下观察肾形态学变化;用TUNEL法检测肾组织细胞凋亡。结果:与肾病组相比,3个干预组中的肌酐、尿素氮、尿蛋白、血压均降低,且差异显著;电镜下肾小球超微结构改善;凋亡细胞减少,差异显著。联合应用组与单用组差异显著。结论:苯那普利、缬沙坦及两者联合应用均可延缓阿霉素肾病肾小球硬化的进展,其机制可能与减少细胞的凋亡及肾超微结构的改善有关,两药联合应用效果更显著。     

Protective Effects of Valsartan and Benazeprilat in Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats

These experiments examined the effectiveness of chronic blockade of the renin angiotensin system with either valsartan or benazeprilat on survival, blood pressure and end-organ damage in salt-loaded stroke-prone SHR. Valsartan or benazeprilat given continuously by subcutaneous osmotic minipump beginning at 10.5 weeks of age lowered blood pressure, as determined by radiotelemetry, prevented proteinuria, prolonged survival and decreased the severity of histopathological changes in the heart and kidney. These results indicate that angiotensin receptor blockade affords a similar degree of protection as inhibition of angiotensin converting enzyme in salt-loaded stroke-prone SHR. Furthermore, our results are consistent with a primary contribution of angiotensin I1 to the maintenance of blood pressure and support a principal role for angiotensin II-dependent mechanisms in the development of end-organ damage in the salt-loaded strokeprone SHR.     

卡维地洛联合缬沙坦胶囊治疗伴有冠心病的原发性高血压患者临床疗效观察

目的：观察卡维地洛联合缬沙坦胶囊治疗伴有冠心病的高血压患者临床疗效。方法将68例伴有冠心病的高血压患者分为2组,治疗组（采用卡维地洛联合缬沙坦胶囊治疗）34例,对照组（采用卡维地洛治疗）34例,2组治疗均为12周。对治疗前后的血压、心率及冠心病的临床指标进行监测评价。结果治疗12周后所有患者收缩压和舒张压、24h心绞痛发作的频率、持续时间、心肌缺血总负荷（TIB）,都有所下降（P＜0．05）,治疗组较对照组下降更明显（P＜0．05）,与治疗前比较差异有统计学意义。结论卡维地洛联合缬沙坦胶囊协同降压对于伴有冠心病的高血压患者临床疗效好,不良反应低,安全性好。     

Haemodynamic effects of valsartan in acute renal ischaemia/reperfusion injury.

BACKGROUND: Acute deterioration of renal function is an important side-effect of angiotensin-converting enzyme (ACE) inhibitors, especially if accompanied by other nephrotoxic events. Angiotensin II receptor(1) blockers (ARB) are thought to have fewer side-effects on renal perfusion and function. We examined the effects of valsartan (VAL) on kidney function as well as the contribution of the nitric oxide (NO) system in a rat model of ischaemic acute renal failure (ARF). METHODS: ARF was induced by 40 min of clamping of both renal arteries in female Sprague-Dawley rats. Renal haemodynamic and tubular parameters were determined during post-ischaemic infusion of vehicle, VAL, VAL and the NO-synthase substrate L-arginine, and VAL together with inhibition of NO synthases (NOS) by L-NMMA. RESULTS: Clamping induced acute renal failure with marked decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) accompanied by a rise in renal vascular resistance (RVR) and fractional sodium excretion. Valsartan caused a slight but significant improvement of GFR and RPF without full recovery of renal function and caused a lowering of RVR and tubular sodium loss. L-arginine-co-administration had no additive beneficial effect. Valsartan-induced changes were not significantly depressed by unspecific inhibition of NOS. CONCLUSIONS: Inhibition of the angiotensin II-receptor(1) diminishes the deleterious effects of ischaemia and reperfusion on glomerular function and on the renal microcirculation. An involvement of the NO system could not be demonstrated.     

黄葵胶囊联合缬沙坦和雷公藤多苷对早期糖尿病肾病患者临床研究

目的：探讨黄葵胶囊联合缬沙坦和雷公藤多苷对早期糖尿病肾病患者临床研究。方法：选择我院于2017年5月至2019年5月期间收治的早期糖尿病肾病患者142例,依据随机表法随机分为观察组71例与对照组71例。对照组患者采用缬沙坦联合雷公藤多苷片治疗,观察组在对照组基础上结合黄葵胶囊。两组疗程均为12周。比较两组治疗疗效,治疗前后尿白蛋白排泄率(UAFR)和肾功能、炎症因子、转化生长因子-β1(TGF-β1)、肾损伤因子-1(Kim-1)和中性粒细胞明胶酶相关载脂蛋白(NGAL)变化,及不良反应。结果：观察组总有效率(91.55%)高于对照组(76.06%)(P<0.05)。观察组治疗后UAFR、Scr和BUN水平低于对照组(P<0.05)。观察组治疗后TNF-α、MCP-1和IL-6水平低于对照组(P<0.05)。观察组治疗后TGF-β1、Kim-1和NGAL水平低于对照组(P<0.05)。观察组不良反应(11.27%)少于对照组(28.17%)(P<0.05)。结论：黄葵胶囊联合缬沙坦和雷公藤多苷对早期糖尿病肾病患者疗效良好,可改善患者肾功能,减轻炎症反应,下调TGF-β1、Kim-1和NGAL水平,且无明显不良反应,用药安全性良好。     

沙库巴曲缬沙坦联用法舒地尔治疗冠心病心力衰竭的临床观察

目的 观察沙库巴曲缬沙坦联用法舒地尔治疗冠心病心力衰竭的临床效果。方法 选取于延安市人民医院心内科住院的冠心病心力衰竭患者80例,随机分成对照组和观察组各40例,均接受常规治疗,对照组采用沙库巴曲缬沙坦治疗,观察组采用沙库巴曲缬沙坦联用法舒地尔,比较两组患者的临床疗效、治疗前后左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、血浆脑钠肽(NT-proBNP)、血清可溶性细胞间黏附分子-1(sICAM-1)和血浆内皮微粒(EMPs)水平及不良反应。结果 观察组总有效率高于对照组,差异有统计学意义(P＜0.05)。治疗前,两组患者LVEDD、LVESD、LVEF、NT-proBNP、EMPs、sICAM-1对比,差异无统计学意义(P＞0.05);治疗后,两组患者LVEDD、LVESD、LVEF、NT-proBNP、EMPs、sICAM-1均较本组治疗前明显改善,且观察组改善更显著,差异有统计学意义(P＜0.05)。两组患者不良反应发生率低。结论 沙库巴曲缬沙坦联用法舒地尔治疗冠心病心力衰竭的临床效果显著,可抑制心肌重塑,降低炎症因子水平,改善心功能,安全性高。     

缬沙坦联合血液透析治疗尿毒症合并顽固性高血压的临床效果

目的探讨缬沙坦联合血液透析治疗尿毒症合并顽固性高血压的临床效果。方法选择2017年5月至2018年5月我院收治的尿毒症合并顽固性高血压患者82例为研究对象,将患者按照不同治疗方式分为参照组(n=41)与联合治疗组(n=41)。参照组采用血液透析治疗,联合治疗组采用缬沙坦联合血液透析治疗。比较两组患者治疗前、治疗1个月后尿蛋白(Upro)、血尿素氮(BUN)、尿微量白蛋白(mALB)水平及临床疗效。结果治疗1个月后,两组患者的Upro、BUN水平均高于治疗前,mALB水平低于治疗前,且联合治疗组优于参照组(P<0.05)。联合治疗组的治疗总有效率高于参照组(P<0.05)。结论缬沙坦联合血液透析治疗尿毒症合并顽固性高血压的临床效果显著,值得临床推广应用。