肾素-血管紧张素-醛固酮系统抑制剂的作用机制

肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system,RAAS)是一种调控心血管和肾功能的复杂的网络系统。RAAS的激活在高血压、急性心肌梗死后的心肌重塑、急性和慢性心力衰竭以及肾功能不全等多种疾病的进展中起着重要的作用,而RAAS抑制剂能够显著延缓上述疾病的进展和改善患者的预后。本文就目前临床常用的几类RAAS抑制剂的作用机制作一概述。     

氨氯地平剂量对高血压患者肾素-血管紧张素-醛固酮系统的影响

目的　观察不同剂量氨氯地平对高血压患者肾素-血管紧张素-醛固酮系统的影响。方法　坐位舒张压95~115mmHg的原发性高血压病人31例,经1周药物洗脱期, 2周安慰剂期后, 口服氨氯地平5mg,qd, 4周末坐位DBP≥90mmHg者剂量加倍×4周。测定安慰剂期后和治疗4, 8周后,立位血管紧张素原(AO)、血浆肾素活性(PRA)、血管紧张素II(AgII)和醛固酮水平(ALD)。结果　6例服氨氯地平每日5mg, 25例需加量至每日10mg。每日5mg氨氯地平使PRA无显著性变化[ (1. 75±3. 22)vs(2. 16±2. 89)ng·(mL·h)-1;P>0. 05],而每日10mg氨氯地平使PRA显著升高[ ( 2. 08±2. 01 ) vs( 4. 63±2. 01)ng·(mL·h)-1,P<0. 01]。2剂量均使AO显著升高(P<0. 01);AgII和ALD均无显著性变化(P>0. 05)。结论　原发性高血压患者服用氨氯地平每日5mg,对PRA无明显影响;而每日服10mg使PRA显著升高。但2剂量对AngⅡ和ALD水平影响均不明显。     

间歇缺氧、睡眠剥夺大鼠血浆肾素、血管紧张素Ⅱ、醛固酮的含量变化

目的采用间歇缺氧、睡眠剥夺建立睡眠呼吸暂停综合征动物模型,观察间歇缺氧、睡眠剥夺对SD大鼠血浆肾素、血管紧张素Ⅱ、醛固酮的影响,探讨间歇缺氧、睡眠剥夺引起睡眠呼吸暂停综合征的机制。方法选取SD雄性青年3个月龄大鼠16只,随机分为2组,分别是间歇缺氧睡眠剥夺组,常氧正常睡眠对照组,每组8只。实验组动物每天给予间歇性缺氧和睡眠剥夺,时间为8周。实验终点测量大鼠有创动脉压,取血测定血浆肾素、血管紧张素Ⅱ、醛固酮水平。结果实验组有创动脉压明显高于对照组,差异有非常显著意义（P〈0．01）;实验组血浆肾素、血管紧张素Ⅱ、醛固酮水平均高于对照组,差异有非常显著意义（P〈0．01）。结论类似睡眠呼吸暂停综合征病理生理改变的间歇性缺氧、睡觉剥夺可以引起SD大鼠血压增高,血浆肾素、血管紧张素Ⅱ、醛固酮水平增高。     

代谢综合征患者血清肾素-血管紧张素-醛固酮水平及临床意义

目的 探讨代谢综合征(metabolic syndrome,MS)患者血清肾素(REN)、血管紧张素(Ang)、醛固酮(ALD)的水平及其与临床检测指标的相关性.方法 选择2014年2月—2016年6月120例MS住院患者为MS组和120例正常体检者为对照组.对两组的血清REN、Ang、ALD、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、餐后2 h血糖(PBG2h)和体重指数(BMI)等进行检测并比较.结果 MS组血清REN、AngⅠ、AngⅡ、ALD、TG、TC、LDL-C、FPG、PBG2h、BMI水平以及高血压和高血糖明显高于对照组(P<0.01),而HDL-C低于对照组(P<0.01).MS患者血清AngⅡ与HDL-C负相关(r=-0.256,P=0.007),与TG、TC、BMI、FPG、PBG2h和高血压呈正相关(r=0.920、0.410、0.310、0.410、0.423和0.568,P均<0.01).结论 REN、Ang和ALD在MS组患者血清中水平较高,可能与MS的发生与发展有关.     

肾素-血管紧张素-醛固酮系统阻滞剂在糖尿病心血管并发症中的应用

糖尿病是心血管疾病的独立危险因素，肾素-血管紧张素-醛固酮系统(RAS)在糖尿病心血管并发症的发生和发展中扮演重要的角色。RAS阻滞剂可分为肾素拮抗剂、血管紧张素转化酶抑制剂、血管紧张素Ⅱ受体拮抗剂和醛固酮拮抗剂。这些药物在不同的水平阻断RAS，可以有效地减少糖尿病心血管系统并发症。     

局部肾素-血管紧张素-醛固酮系统弓糖尿病肾病的治疗

循环中肾素-血管紧张素-醛固酮系统（RAAS）成分由分布于全身的组织细胞合成与分泌。糖尿病时，肾脏局部肾素、血管紧张素（Ang）Ⅱ、醛固酮等活性增加，它们作用于血管或通过激活炎症因子等途径，导致肾血管病变及肾纤维化。动物试验与临床研究表明，抑制RAAS可延缓糖尿病肾病进程。     

局部肾素-血管紧张素-醛固酮系统与糖尿病肾病的治疗

循环中肾素-血管紧张素-醛固酮系统(RAAS)成分由分布于全身的组织细胞合成与分泌.糖尿时,肾脏局部肾素、血管紧张素(Ang)Ⅱ、醛固酮等活性增加,它们作用于血管或通过激活炎症因子等途径,导致肾血管病变及肾纤维化.动物试验与临床研究表明,抑制RAAS可延缓糖尿病肾病进程.     

肾素-血管紧张素-醛固酮系统与妊娠高血压病的关系

目的探讨肾素-血管紧张素-醛固酮系统(RAAS)与妊娠高血压疾病(HDCP)的关系。方法选取2014年2月~2015年8月在我院住院分娩的孕产妇92例,其中合并HDCP 38例,设为妊高症组,正常孕产妇54例,设为对照组。比较两组孕产妇产前、产后血浆活性肾素(PRA)水平、血管紧张素Ⅱ(AngⅡ)及醛固酮(ALD)水平的差异。结果与对照组比较,妊高症组孕产妇产前血浆PRA、AngⅡ水平均明显降低(P<0.05),ALD水平明显升高(P<0.05);与产前比较,妊高症组孕产妇产后血浆PRA、AngⅡ均明显升高,ALD水平明显降低(P<0.05),而对照组无统计学差异(P>0.05);与对照组比较,妊高症组孕产妇产后AngⅡ水平明显升高(P<0.05),而PRA、ALD水平比较差异无显著性(P>0.05);妊高症组孕产妇胎盘组织中AT1受体表达明显强于对照组(P<0.05),组间肾素表达差异无统计学意义(P>0.05)。结论 HDCP的发病与胎盘组织局部肾素-血管紧张素系统相关,其机制可能与胎盘组织中AT1受体表现显著增多,通过多种途径影响胎盘血流灌注,使胎盘发生缺血缺氧有关。     

阻断肾素-血管紧张素-醛固酮系统不同环节对大鼠肝纤维化的影响

目的 探讨阻断肾素-血管紧张素-醛固酮系统(RAAS)不同环节对大鼠实验性肝纤维化的影响.方法 6周龄SD大鼠50只随机均分为空白对照(BC)组、模型对照(MC)组和A、B、C三个药物处理组.BC组腹壁皮下注射橄榄油;其余4组注射40％ CC14制备大鼠肝纤维化模型.次日,A组胃内灌注卡托普利60 mg/kg,B组胃内灌注氯沙坦10mg/kg,C组胃内灌注螺内酯100 mg/kg,1次/d;第8周处死,取材,HE染色和Masson染色观察肝组织病理变化,免疫组化、RT-PCR 及Western blot法检测肝组织转化生长因子β1(TGF-β1)表达.结果 A、B、C组肝纤维化程度均明显较MC组减轻(P＜0.05).MC组TGF-β1表达明显高于BC组(P＜0.05)和A、B、C组(P＜0.05),但A、B、C组三组间无明显差异.结论 阻断RAAS不同环节均可抑制肝纤维化形成,其作用可能与其降低TGF-β1表达有关.     

钠盐及其调控因素对骨骼影响的研究进展

高盐的摄入可以引发高血压已有很多研究,随着研究的深入,越来越多的证据表明高盐的摄入还引起骨量丢失,导致骨质疏松和骨折。Na+在生理和病理过程中起着很重要的作用,细胞凋亡、肿瘤生长以及离子转运都与细胞内外的Na+有关,而且Na+与骨骼的关系目前越来越受到关注。该文综述了钠盐及其调控因素:Na+,K+-ATP酶、钠氯共同转运体(NCC)、上皮钠离子通道(ENaC)、肾素-血管紧张素-醛固酮系统(RAAS)对骨骼的影响。     

A physiologically based kinetic (PBK) model describing plasma concentrations of quercetin and its metabolites in rats

Biological activities of flavonoids in vivo are ultimately dependent on the systemic bioavailability of the aglycones as well as their metabolites. In the present study, a physiologically based kinetic (PBK) model was developed to predict plasma concentrations of the flavonoid quercetin and its metabolites and to tentatively identify the regiospecificity of the major circulating metabolites. The model was developed based on in vitro metabolic parameters and by fitting kinetic parameters to literature available in vivo data. Both exposure to quercetin aglycone and to quercetin-4′-O-glucoside, for which in vivo data were available, were simulated. The predicted plasma concentrations of different metabolites adequately matched literature reported plasma concentrations of these metabolites in rats exposed to 4′-O-glucoside. The bioavailability of aglycone was predicted to be very low ranging from 0.004%-0.1% at different oral doses of quercetin or quercetin-4′-O-glucoside. Glucuronidation was a crucial pathway that limited the bioavailability of the aglycone, with 95–99% of the dose being converted to monoglucuronides within 1.5–2.5 h at different dose levels ranging from 0.1 to 50 mg/kg bw quercetin or quercetin-4′-O-glucoside. The fast metabolic conversion to monoglucuronides allowed these metabolites to further conjugate to di- and tri-conjugates. The regiospecificity of major circulating metabolites was observed to be dose-dependent. As we still lack in vivo kinetic data for many flavonoids, the developed model has a great potential to be used as a platform to build PBK models for other flavonoids as well as to predict the kinetics of flavonoids in humans.     

Effect of high salt intake on local renin-angiotensin system and ventricular dysfunction following myocardial infarction in rats

1. This study was performed to evaluate the effect of chronic high salt intake on local cardiac and renal components of the renin-angiotensin system (RAS) and its impact on cardiac remodelling and function after myocardial infarction (MI). 2. Rats submitted to coronary artery ligation to produce MI or sham operation (SO) were randomized to receive 1% NaCl solution or tap water as drinking water for 4 weeks. Plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) activity were quantified. Tissue angiotensin (Ang) II and ACE activity were determined by ELISA and a fluorimetric assay, respectively. Renal and cardiac AT(1) and AT(2) receptor protein levels were quantified by western blot. 3. Independent of the lower PRA levels, MI promoted a significant increase in the left ventricular/bodyweight ratio and impaired cardiac function. The cardiac RAS was activated after MI with a significant increase in ACE activity, AngII and AT(1) receptor levels. The RAS was slightly attenuated under high-salt conditions. 4. Interestingly, high salt intake increased the expression of the AT(2) receptor by approximately twofold in the kidney of MI rats compared with the SO control group. Because of its natriuretic effect, the AT(2) receptor may counterbalance the salt overload and prevent the additional impairment of cardiac function. 5. The present study indicates that 4 weeks after MI, high salt intake did not further increase cardiac hypertrophy or further impair cardiac function in MI rats. A chronic increase in salt intake significantly suppressed PRA, but did not prevent activation of the local RAS or the progression of cardiac remodelling and left ventricular dysfunction caused by MI. 6. The present results show that inhibition of systemic renin production with salt overload does not affect ventricular remodelling after MI in rats. This suggests that local activation of the RAS in the heart, which was not suppressed by salt overload, exerts a predominant role for local adaptations of the heart after MI.     

Biliary excretion of pravastatin and taurocholate in rats with bile salt export pump (Bsep) impairment

The bile salt export pump (BSEP) is expressed on the canalicular membrane of hepatocytes regulating liver bile salt excretion, and impairment of BSEP function may lead to cholestasis in humans. This study explored drug biliary excretion, as well as serum chemistry, individual bile acid concentrations and liver transporter expressions, in the SAGE Bsep knockout (KO) rat model. It was observed that the Bsep protein in KO rats was decreased to 15% of that in the wild type (WT), as quantified using LC–MS/MS. While the levels of Ntcp and Mrp2 were not significantly altered, Mrp3 expression increased and Oatp1a1 decreased in KO animals. Compared with the WT rats, the KO rats had similar serum chemistry and showed normal liver transaminases. Although the total plasma bile salts and bile flow were not significantly changed in Bsep KO rats, individual bile acids in plasma and liver demonstrated variable changes, indicating the impact of Bsep KO. Following an intravenous dose of deuterium labeled taurocholic acid (D4‐TCA, 2 mg/kg), the D4‐TCA plasma exposure was higher and bile excretion was delayed by approximately 0.5 h in the KO rats. No differences were observed for the pravastatin plasma concentration–time profile or the biliary excretion after intravenous administration (1 mg/kg). Collectively, the results revealed that these rats have significantly lower Bsep expression, therefore affecting the biliary excretion of endogenous bile acids and Bsep substrates. However, these rats are able to maintain a relatively normal liver function through the remaining Bsep protein and via the regulation of other transporters. Copyright © 2016 John Wiley & Sons, Ltd.     

氢氧化钠质量标准中钾盐、铝盐检查项的探讨与研究

目的:探讨《中国药典》2020年版四部氢氧化钠标准中钾盐、铝盐检查项目的合理性和修订意见。方法:寻找灵敏度更高、专属性更强和操作更简便的方法,对钾盐和铝盐进行检查。结果:四苯硼钠方法检查钾盐,灵敏度更高。采用专属性更强的铝试剂检验方法,替代炽灼残渣方法检测铝盐。结论:本文建立的方法能对钾盐和铝盐进行更灵敏,专属性更强的检验,操作简便。     

丙戊酸钠对重度烫伤大鼠心肌保护作用及其机制研究

目的研究丙戊酸钠(抗癫痫药)对重度烫伤大鼠心肌保护作用及其机制。方法 98只♂SD大鼠,随机分为4组:①假烫组、②烫伤组、③烫伤+二甲基二乙酸(2M2P)组和④烫伤+丙戊酸钠(VPA)组,80℃水浴(假烫组37℃),造成50%总体表面积(TBSA)Ⅲ度烫伤。③、④组分别于烫伤后,即刻皮下注射2M2P、VPA300 mg.kg-1。分别于烫伤后2,6 h腹主动脉取血,测定磷酸肌酸激酶同工酶(CK-MB)变化;然后处死大鼠观察心肌病理变化;检测心肌热休克蛋白(HSP70)表达。结果烫伤大鼠血浆CK-MB水平持续升高,于伤后6 h,VPA组的血浆CK-MB水平(U.L-1)显著低于烫伤组(4398.0±1273.8 vs5438.0±987.9,P<0.01)和2M2P组(4398.0±1273.8 vs 5198.0±1097.3,P<0.01),HSP70表达明显高于烫伤组和2M2P组。病理观察显示,VPA组的心肌损伤轻于烫伤组和2M2P组。结论 VPA改善烫伤休克大鼠心肌酶学指标和组织学损伤,其机制可能与其促进保护性蛋白HSP70表达增多有关。     

Qi盐对正常及糖尿病模型大鼠血糖的影响

目的观察Qi盐对正常小鼠和糖尿病模型大鼠的降血糖作用.方法尾静脉注射四氧嘧啶制作大鼠糖尿病模型,连续灌胃给Qi盐14 d,葡萄糖氧化酶法测血糖.结果Qi盐1.6,0.8,0.4 g·kg-1对正常小鼠血糖及糖耐量均无明显影响,但0.8,0.4 g·kg-1可降低四氧嘧啶模型大鼠血糖,改善糖耐量.结论Qi盐对糖尿病模型大鼠有降血糖作用.     

Qi盐对肾性和自发性高血压大鼠血压的影响

目的观察Qi盐对肾性和自发性高血压大鼠(SHR)的降压作用.方法通过缩窄左肾动脉而制备2K1C夹的肾性高血压模型,同时选用16周龄的SHR,2种实验鼠均连续给予Qi盐0.4、0.2、0.1 g·kg-1,14 d(ig,qd),观察其对肾性和SHR BP的影响.结果Qi盐各剂量组及普通盐组对肾性高血压模型鼠BP在用药d 7、14均无明显的影响,而对SHR,Qi盐0.4、0.2 g·kg-1给药7d后可显著降低BP,与对照组相比,P<0.05,但14 d后BP有所回升.结论Qi盐对肾性高血压模型无明显的治疗作用,但在给药7 d后能显著地降低SHR的BP.