EFFECTS OF LOSARTAN ON THE CARDIOVASCULAR SYSTEM, RENAL HAEMODYNAMICS AND FUNCTION AND LUNG LIQUID FLOW IN FETAL SHEEP

1. The angiotensin type 1 (AT₁) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125–132 days gestation). Losartan reduced the fetal systolic (P < 0.01) and diastolic (P < 0.01) pressor response to 5 μg angiotensin II (AngII) i.v. from 27.4 ± 1.5 to 7.4 ± 0.9 and from 17.5 ± 1.3 to 5.4 ± 0.6 mmHg, respectively, after 1h and to 6.1 ± 0.5 and 4.4 ± 0.5 mmHg, respectively, after 2h. Maternal pressor responses to 5 μg AngII i.v. were unchanged. Fetal mean arterial pressure decreased (P < 0.05) after losartan administration, but fetal heart rate did not change. 2. Fetal haematocrit increased (P < 0.05), fetal PO₂ decreased (P < 0.01), PCO₂ did not change and pH decreased (P < 0.01), as did plasma bicarbonate levels (P < 0.01) following administration of losartan. Thus, losartan induced a fetal metabolic acidosis. 3. Fetal placental blood flow did not change following administration of losartan. In the fetal kidney, losartan caused a decrease in vascular resistance (P < 0.01) and an increase in blood flow (P < 0.05). Glomerular filtration rate decreased (P < 0.05); thus, filtration fraction decreased (P < 0.01). There was no change in the fractional reabsorption of sodium and glomerulotubular balance was maintained. Free water clearance decreased (P < 0.01) and became negative. Urine flow decreased (P < 0.01), the excretion rates of sodium, potassium and chloride did not change, but the urinary sodium:potassium ratio decreased (P < 0.05). There was a decrease in lung liquid flow (P < 0.05) following losartan. 4. It is concluded that the fetal renin-angiotensin system (RAS) is important in the maintenance of fetal arterial pressure, the regulation of fetal renal blood flow and is essential in the maintenance of fetal glomerular function. Further, these actions of AngII are mediated via functional AT₁ receptors. These effects of losartan on the fetal cardiovascular system, renal blood flow and function are similar to those observed following captopril administration. Thus, the effects of angiotensin converting enzyme (ACE) inhibition in the foetus are due to the blockade of the fetal RAS and are independent of any direct effects on bradykinin or prostaglandin levels.     

Deleterious effect of exogenous angiotensin-I on the extent of regional ischaemia and its inhibition by captopril

The endogenous activity of the local renin-angiotensin system(RAS) and the anti-ischaemic properties of captopril were investigatedin electrically driven rabbit Langendorff hearts (constant pressure:70 cmH₂O, Tyrode solution, Ca²⁺ 1.8 mmol.l^–1). Cumulativeconcentration-response curves showed no significant difference(P>0.05) between the reduction of the global coronary flow(CF) by exogenous angiotensin-I or angiotensin-II (EC₅₀ = 10^–10mol.l^–1). It is concluded that the local RAS in isolatedrabbit hearts is highly sensitive, whereas its endogenous activityis very low due to very low endogenous angiotensin-I content.Myocardial ischaemia (MI) was induced by the occlusion of aleft coronary artery branch and MI was quantified from NADHsurface fluorescence photography. MI was significantly enlarged(+35%) (P <0.05) by exogenous angiotensin-I (6x10^–9mol.l^–1). The reduction in CF and the increment in MIby angiotensin-I could be completely prevented by adding captoprilat a low concentration (10^–6 mol.l^–1) to the perfusionbuffer. In the absence of exogenous angiotensin-I, captoprilalone (10^–6 mol.l^–1) neither significantly enhancedCF (P >0.05), nor diminished MI (P >0.05), supportingthe finding of very low endogenous activity of tile local RASin this model. We, moreover, conclude that at a low concentration(10^–6 mol.l^–1) captopril does not possess directcardioprotective properties independent of its ACE inhibitingaction.     

心包肽类激素免疫组织化学及免疫电镜的研究

采用免疫组织化学、免疫电子显微镜及高效液相结合放射免疫学方法,研究人和 Wistar 大鼠心包,结果表明:心包组织中存在 ANF 和 AngⅡ样物质。在采用兔抗 ANF 为抗体时,心包组织的间皮细胞存在明显的金粒子标记颗粒,间皮细胞是主要的内分泌细胞。心包组织存在 Ang Ⅱ和3种分子形式ANF.本研究提示.心包除已知功能外,尚存在重要的内分泌功能.     

退行性腰椎管狭窄症相关指南的质量评价和推荐意见比较研究

背景 退行性腰椎管狭窄症（DLSS）是一种老年多发,严重影响患者正常生活且医疗费用负担较重的疾病。DLSS治疗方法较多,开发高质量的临床实践指南和临床医生应用高质量指南是提高DLSS诊疗水平的重要途径。目的 采用AGREEⅡ及RIGHT评价DLSS相关指南的方法学及报告质量,为DLSS指南制订及报告提供参考依据。方法 计算机检索中国生物医学文献数据库（CBM）、中国知网（CNKI）、万方数据知识服务平台（Wanfang Data）、维普网（VIP）、PubMed,补充检索医脉通数据库（Medlive）、世界卫生组织（WHO）、英国国家临床优化研究所（NICE）、国际指南协作网（GIN）、美国国立指南文库（NGC）和苏格兰院际间协作网（SIGN）等指南库中有关DLSS的临床实践指南、共识或规范,检索时限均为2010-01-01至2022-01-01。由两位评价员独立对纳入文献进行方法学质量及报告质量评价,并在文献中推荐意见等级统一前提下进行比较。结果 共纳入6篇文献,其中4篇指南,2篇共识;1篇指南为中医指南,3篇指南为循证指南。AGREEⅡ评价结果显示纳入6篇文献的实际总得分/总最高可...     

小儿遗尿症指南和专家共识质量评价

背景 小儿遗尿症是儿科常见病之一,有效的小儿遗尿症诊疗指南有助于症状的规范化控制和缓解,而制定高质量的临床实践指南是提高小儿遗尿症诊疗水平的重要方式。目的 基于AGREEⅡ和RIGHT工具,评价2010年以来国内外发布的小儿遗尿症指南和专家共识的质量,以期为临床实践及后续指南的制订提供参考。方法 检索中国知网、万方数据知识服务平台、维普网、中国生物医学文献数据库和PubMed(补充检索医脉通、世界卫生组织以及英国国家临床示范研究所等数据库)2010-01-01至2022-01-31公开发表的小儿遗尿症相关的诊疗指南和专家共识。采用AGREEⅡ和RIGHT工具评价纳入文献的方法学和报告质量。根据AGREE Ⅱ工具评价结果,将各指南/共识推荐等级评定为“推荐(A级)”“更新后推荐(B级)”和“不推荐(C级)”。使用组内相关系数(ICC)进行一致性评价。结果 纳入8部指南和5部专家共识。共形成推荐意见185条,其中44条为诊断评估方面的意见,140条为治疗方面的推荐意见,1条为随访推荐意见。AGREEⅡ工具评价结果显示,范围和目的、参与人员、严谨性、清晰性、应用性和独立性6个领域的总得分(报...     

脓毒症患者外周血单核细胞miR-147b的表达及其与病情严重程度和预后的关系

目的 探讨脓毒症患者外周血单核细胞miR-147b的表达水平及其与病情严重程度及预后的相关性。方法 选择2019年1月至2021年6月于安徽医科大学第一附属医院就诊的46例脓毒症患者(脓毒症组)和50例普通感染患者(普通感染组)作为研究对象。查阅患者病历,记录年龄、性别、感染部位等一般资料。采用酶联免疫吸附试验试剂盒检测研究对象血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和C反应蛋白(C-reactive protein, CRP)的浓度。计算序贯性器官衰竭评分(sequential organ failure score, SOFA)和急性生理学与慢性健康状况评分Ⅱ(acute physiology and chronic health scoreⅡ,APACHEⅡ)。观察或随访脓毒症患者的28 d预后情况,分为生存组和死亡组。应用逆转录聚合酶链反应测定外周血单核细胞中miR-147b的表达水平。结果 脓毒症组和普通感染组的年龄、性别、感染部位分布比较差异无统计学意义(P>0.05)。脓毒症组患者的TNF-α、CRP水平、SOFA评分和A...     

Lack of association of angiotensin I-converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians

Eighty-five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early-onset MI was found in this population group. Other gene components of the renin-angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.     

血管紧张素Ⅱ受体1和受体2在小鼠肾脏发育中的表达

目的观察小鼠肾脏发育中血管紧张素Ⅱ受体1(AngiotensinⅡreceptor type1,AT_1)和受体2 (AT_2)的表达特征,探讨小鼠肾脏发育过程中AT_1和AT_2的作用及相互关系。方法应用免疫组织化学技术、免疫印迹法(Western blot)并结合体视学方法检测胚龄12、14、15、16、18d及生后日龄1、3d小鼠肾脏发育中AT_1和AT_2的表达。结果AT_1和AT_2均首先出现在输尿管芽,然后出现在肾小管,生后表达逐渐减弱。早期肾小体内AT_2丰富表达,随着肾小体的成熟表达量逐渐降低。结论在小鼠肾脏发育中,AT_1可能与输尿管芽分支不断延长以及肾小管的增殖密切相关,AT_2可能与输尿管芽和肾小体的相互诱导相关。     

菊藤胶囊对应激大鼠血压、血浆血管紧张素Ⅱ和血液流变学的影响

目的观察中药复方菊藤胶囊对慢性应激性高血压大鼠血压、血浆血管紧张素Ⅱ（AngⅡ）及血液流变学的影响。方法大鼠随机分为6组（每组7只）：应激＋蒸馏水组（model），应激＋菊藤胶囊高剂量组（JT—H），应激＋菊藤胶囊中剂量组（JT—M），应激＋菊藤胶囊低剂量组（JT—L），应激＋卡托普利组（captopril），正常对照组（control）；除正常对照组外，其余5组均采用低频低压交流电间断电击法。电击大鼠足底28d，制作应激性高血压模型，同时各组均加入不同的干预。后应用经尾动脉测量血压和心率，酶联免疫吸附法（ELISA）检测大鼠血浆血管紧张素Ⅱ，血液流变学和细胞流变学的各项指标。观察比较菊藤胶囊不同剂量组、卡托普利组对应激致大鼠血压及相关指标的影响。结果与正常对照组相比，模型组大鼠血压和血浆血管紧张素Ⅱ含量明显升高（P〈0．01）。全血黏度、血浆黏度、纤维蛋白原及红细胞聚集指数均明显升高（P〈0．05），红细胞变形指数无变化。与模型组相比，菊藤胶囊高、中组均能抑制应激大鼠的血压及血浆血管紧张素Ⅱ含量的升高（P〈0．01），菊藤胶囊高剂量能明显改善应激大鼠的血液流变性（P〈0．05），低剂量组应激大鼠的血液流变学无明显改变（P〉0．05）。结论菊藤胶囊能够降低应激性高血压大鼠的血压，其机理可能是通过降低血浆中血管紧张素Ⅱ的含量和改善血液流变和细胞流变性实现的。     

核因子-κB在血管紧张素II介导的大鼠胰腺纤维化发生中的作用

目的 :探讨NF -κB在血管紧张素II介导的大鼠胰腺纤维化发生中的作用。方法 :SD大鼠 (2 0 0 -30 0g)随机分为正常组、对照组、治疗组。大鼠胰管内逆行注射 2 %三硝基苯磺酸 (TNBS)复制胰腺纤维化模型。于造模后第 1d始 ,治疗组给予洛沙坦灌胃 (10mg·kg-1·d-1) ,模型组给予等量的无菌蒸馏水。分别采用免疫印迹、免疫组化和TransAMTM方法检测胰腺组织NF -κB表达、分布和活化情况。采用硫堇蓝 (toluidineblue)染色和透射电镜观察肥大细胞数量、分布和活化脱颗粒现象。RT -PCR研究胰腺组织细胞间粘附分子 (ICAM - 1)mRNA表达。结果 :造模后第 3d大鼠胰腺组织NF -κBp6 5蛋白表达及其活性增加 ,第 7d达峰值 [(0 4 0 6± 0 0 86 )mg/g总蛋白 ]。对照组大鼠胰腺组织中肥大细胞活化 ;ICAM - 1mRNA表达于第 3d和第 7d增加。洛沙坦可抑制NF -κB蛋白表达和肥大细胞活化、下调ICAM - 1mRNA表达。结论 :血管紧张素II在大鼠胰腺纤维化形成早期可能通过受体AT1途径促发炎症反应及纤维化 ,具体机制可能与NFκB表达增加并活化有关