摘要目的 观察连续性血液透析滤过(CVVHDF)治疗犬多器官功能不全综合征(MODS)过程中肾素-血管紧张素系统(RAS)及血管紧张素转化酶2(ACE2)-血管紧张素(1-7)[Ang(1-7)]-Mas轴成员的动态变化,探讨CVVHDF治疗MODS过程中ACE2-Ang(1-7)-Mas轴对心脏功能的影响及疗效作用机制.方法 经失血性休克+复苏灌注+内毒素血症建立犬MODS模型,按照随机数字表进行随机分组,分为CVVHDF组(n=8)和MODS组(n-6).内毒素注射完毕后CVVHDF组接受CVVHDF治疗12 h;MODS组不给予治疗.测定各时间点器官功能;用放射免疫法、酶联免疫法测肾素、AngⅠ、AngⅡ、Ang(1-7)含量;实时定量PCR法测肾素、ACE2mRNA表达;Western印迹法测肾素、AngⅡ、ACE2及Ang(1-7)蛋白表达.结果 (1)器官功能:经CVVHDF治疗后,CVVHDF组犬生命体征逐渐趋于平稳,心功能、肺功能、肾功能较MODS组均有所改善,两组差异有统计学意义(P＜0.05).(2)RAS指标变化:经CVVHDF治疗后,从器官水平、基因水平、分子水平检测相应指标发现,CVVHDF组心房肌组织中肾素、Ang Ⅰ、AngⅡ含量,肾素mRNA表达,肾素、AngⅡ蛋白含量,均低于MODS组,两组差异有统计学意义(P＜0.01).(3)ACE2-Ang(1-7)-Mas轴的变化:经CVVHDF治疗后,从器官水平、基因水平、分子水平检测相应的指标发现,CVVHDF组心房肌组织中Ang(1-7)含量、ACE2mRNA表达、ACE2及Ang(1-7)蛋白含量,均高于MODS组,两组差异有统计学意义(P＜0.01).结论 CVVHDF治疗MODS过程中,ACE2-Ang(1-7)-Mas轴与肾素-血管紧张素-醛固酮系统相拮抗,起到保护心肌的作用.这一研究为临床CVVHDF救治MODS提供了强有力的支持.

abstractsObjective To observe the members' dynamic change of renin-angiotensin system (RAS) and angiotensin converting enzyme 2(ACE2)-Ang(1-7)-Mas axis during the continuous venovenous hemodiafiltration (CVVHDF) treating the dogs with multiple organ dysfunction syndrome (MODS),and to investigate the efficacy mechanism on cardiac function.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=8) and MODS group (n=6).After endotoxin injection completion,the CVVHDF group received CVVHDF for 12 h,MODS group didn't.Radioimmunoassay,euzymelinked mmunosorbent assay (ELISA) were used to detect the content of renin,Ang Ⅰ,Ang Ⅱ,Ang (1-7).Real-time PCR was used to detect the expression of renin mRNA and ACE2 mRNA.Western blotting was used to detect the protein content of renin,Ang Ⅱ,ACE2 and Ang (1-7).Results (1) Organ function:Compared with the MODS group,the vital signs,heart,lung and renal function were significantly ameliorated in the CVVHDF group,the difference had statistical significance (P＜ 0.05).(2) RAS changes:To detect index from the level of organs,genetic and molecular in arterial tissue,the results displayed that the content of renin,Ang Ⅰ,Ang Ⅱ,the expression of renin mRNA,the protein content of renin,Ang Ⅱ in CVVHDF group were lower than that in MODS group,the difference had statistical significance (P ＜ 0.01).(3)ACE2-Ang(1-7)-Mas axis's changes:Using the same methods above to detect corresponding indicators,the results displayed that the content of ACE2,Ang(1-7),the expression of ACE2 mRNA and the protein content of ACE2,Ang(1-7) in CVVHDF group were significantly improved than that in MODS group,the difference had statistical significance (P ＜ 0.01).Conclusions In the process of CVVHDF treating MODS,the ACE2 -Ang(1-7)-Mas axis plays the role which antagonizes the RAS system,and to protect the cardiac function.This research may be important for MODS' clinical rescue.