大鼠烧伤早期各内脏内皮素的变化

目的探讨烧伤后内皮素变化及其在内脏损害中的作用。方法采用大鼠30％Ⅲ度烧伤模型动态观察大鼠烧伤后血浆、心、肝、肺、肾脏内皮素的变化规律及应用非选择性内皮素受体拮抗剂PD145065对烧伤大鼠内脏损害的作用。结果正常大鼠4种脏器每克组织中内皮素含量以肺脏最高,其次为肾、肝、心脏,血浆、肝、肾、肺脏内皮素含量伤后2小时均明显升高,6小时达峰值,24小时内仍高于伤前;心脏内皮素含量与上述变化类似,但伤后12小时达峰值,且升高幅度较其它脏器低;肝肾内皮素的升高与伤后相应肝、肾血流量减少呈明显负相关。应用PD145065不仅可使肝、肾血流量显著回升,而且明显降低心、肝、肺、肾脏器含水量,减轻内脏损害。结论烧伤后内皮素的异常改变一定程度上参与了烧伤早期内脏损害。     

Endothelin excretion during ketoacidosis does not correlate with tubular dysfunction

Urinary excretion of endothelin was measured by radioimmunoassay in children with diabetes mellitus during severe ketoacidosis and 12 days later when blood pH and blood glucose concentrations were normal. Metabolically stable diabetic children served as controls. Results from apparently healthy children without diabetes mellitus were used as normal values. Renal tubular injury was evaluated by the urinary excretion of the proximal tubular marker ₁-microglobulin and the distal tubular marker Tamm-Horsfall protein (THP). During ketoacidosis we detected a decreased glomerular filtration rate associated with highly significant changes in the excretion of ₁-microglobulin, indicating proximal tubular damage, and THP, suggesting disturbance of cells of the ascending loop of Henle. The daily excretion of endothelin was unaltered but the ratio of endothelin/creatinine or endothelin excretion/creatinine clearance were significantly enhanced. In conclusion, we could demonstrate that, despite a proximal and distal tubular cell dysfunction, endothelin excretion when related to creatinine clearance may be a consequence of disturbed proximal tubular function or dysfunction of the renal medulla.     

妊高征母血、脐血染色体稳定性和内皮素变化的研究

目的 在致妊高征(PIH)众多因素中,观察PIH孕妇外用血及其脐血姐妹染色单体互换(SCE)频率和内皮素(ET)的变化及其两者的关系,以资探讨PIH的病因和提高PIH的监测水平。方法 采用SCE法和放免法分别对21例PIH病人和15例正常孕妇(对照组)的外周血及其所分娩新生儿脐血SCE频率及其ET进行测定。结果 PIH组外周血和脐血SCE频率分别为6.11±1.29,5.98±1.38;对照组外周血和脐血SCE频率分别为3.45±O.71,3.16±0.57,其两组比较,差异有极显著性(P<0.001)。PIH组外用血和脐血SCE频率皆异常。PIH组外用血ET含量的均值(51.87±24.72pg/ml)明显低于其脐血的均值(63.65±27.63pg/ml),两者比较差异有显著性(P<0.05)。两组SCE和ET相关性分析无明显相关性(r=0.092,P>0.05)。结论 PIH与遗传物质DNA损伤有关,SCE频率可作为一项诊断、预测PIH的重要指标。PIH孕妇脐血ET增高有助于PIH发病机理的揭示。     

高血压病合并左心室增大与内皮素关系研究

目的 为探讨高血压病合并左心室增大与血浆内皮素的关系.方法 用放射免疫法测定高血压病人血浆内皮素水平.结果 高血压病患者血浆ET水平明显高于对照组,而尤以高血压合并左心室增大者更为显著.结论 ET在高血压病的发生和发展中起重要作用.预期内皮素受体桔抗剂具有重要的治疗学价值.     

氯沙坦对原发性高血压患者血管内皮功能的影响

目的 研究氯沙坦对原发性高血压(EH)患者血管内皮功能的影响.方法 分析应用氯沙坦前后EH患者血压、ET(血浆内皮素)及NO(一氧化氮)的变化.结果 EH患者血浆ET升高(P<0.01)、NO降低(P<0.01).应用氯沙坦后,EH患者血压显著下降(P<0.01)、ET明显降低(P<0.01),NO明显升高(P<0.01).结论 氯沙坦可有效降压,并能逆转EH患者血管内皮功能紊乱.     

针刺水沟、风府穴对脑缺血模型大鼠血一氧化氮及内皮素含量的影响

目的 探讨针刺水沟-风府穴组治疗缺血性脑卒中的作用机制。方法 将40只大鼠分为正常组、模型组、水沟-风府组（针刺大鼠水沟、风府穴）、非经非穴组（针刺大鼠臀部两处非经非穴点）,每组10只。采用阻闭大鼠大脑中动脉制备永久性脑缺血模型。72 h后观察各组大鼠神经功能评分,血清一氧化氮及血浆内皮素含量的变化。结果 与模型组比较,水沟-风府组脑缺血大鼠神经功能评分明显降低（P＜0.05）,而非经非穴组无明显变化（P＞0.05）。与模型组比较,非经非穴组大鼠血清一氧化氮及血浆内皮素含量无明显变化（P＞0.05）,水沟-风府组大鼠血清一氧化氮及血浆内皮素含量明显降低（P＜0.05）。结论 针刺水沟-风府穴组对缺血性脑卒中具有明显的改善作用,其机制可能与降低血液中一氧化氮、内皮素的含量有关。     

阿托伐他汀对H型高血压患者同型半胱氨酸、内皮功能和C反应蛋白的影响

目的 分析不同剂量阿托伐他汀对H型高血压患者同型半胱氨酸(Hcy)、内皮功能和C反应蛋白(CRP)的影响.方法 将120例H型高血压患者分为常规治疗组、强化治疗组和对照组,每组40例.3组患者均给予常规降压治疗,常规治疗组和强化治疗组在常规降压治疗基础上分别口服阿托伐他汀20 mg/d和40 mg/d,治疗12周.观察治疗前后患者血脂水平、血压、血清Hcy、内皮素-1(ET-1)、C-反应蛋白(CRP)、NO水平变化.结果 治疗后,常规治疗组和强化治疗组血压较前下降(P＜0.05),血脂水平较前改善(P＜0.05),血清Hcy、ET-1、CRP、NO水平均下降(P＜0.05),并且Hcy、ET-1、CRP及NO水平下降水平高于对照组(P＜0.05);强化治疗组Hcy、ET-1、CRP及NO下降水平高于常规治疗组(P＜0.05).结论 大剂量阿托伐他汀能够降低H型高血压患者血清Hcy水平,抑制炎症反应,改善内皮功能,提高疗效.     

The metabolism of the dual endothelin receptor antagonist macitentan in rat and dog

Abstract

1.?The metabolism of the endothelin receptor antagonist macitentan has been characterized in bile duct-cannulated rats and dogs.

2.?In both species, macitentan was metabolized along five primary pathways, i.e. conjugation with glucose (M9), oxidative depropylation (M6), aliphatic hydroxylation (M7), oxidative cleavage of the ethylene glycol linker (M4) and hydrolysis of the sulfamide moiety (M3). Most of the primary metabolites underwent subsequent biotransformation including conjugation with glucuronic acid or glucose, hydrolysis of the sulfamide group or secondary oxidation of the ethylene glycol moiety.

3.?Though there were species differences in their relative importance, all metabolic pathways were present in rat and dog. The depropylated M6 was the only metabolite present in plasma of both species.

4.?Metabolism was a prerequisite for macitentan excretion as relevant amounts of parent drug were neither detected in bile nor urine. Biliary excretion was the major elimination pathway, while renal elimination was of little importance.