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Objective 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.
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Objective Plasma phospholipid metabolism analysis was employed to investigate plasma metabolic profile of acute renal graft rejection in order to find potential disease biomarkers and reveal its pathophysiological changes.Methods Selected 33 patients which did renal transplant in our hospital during 2009 to 2010,named preoperative group.14 patients were diagnosed as acute graft rejection,and 19 patients were non-acute graft rejection.Then use ultra performance liquid chromatography (UPLC) coupled with quadrupole time of flight mass spectrometry (qTOF-MS) to establish the metabolic fingerprint in those patients.The date was preprocessed with software Markerlynx,and analyzed with partial least squares discriminant analysis (PLS-DA),and data from conventional laboratory techniques were used for assessing renal function.Results In the plasma of renal transplant patients,seventeen biomarkers were discovered:creatinine,four sphingomyelins (SM),nine phosphatidylcholines (PC),three lysophosphatidylcholine (LPC).While the creatinine was increased,the others were reduced obviously.Conclutions UPLC-qTOF-MS based metabonomics can analyze the plasma phospholipid metabolism in patients with renal transplantation,reveal the law of phospholipids metabolic changes in the process of acute rejection.The levels of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation are increased.The immunosuppressive therapy can reduce the activity of phospholipase,inhibit the level of plasma phosphatidylcholine's esterlysis and fatty acids' β-oxidation,which restraines the development of acute rejection after renal transplantation.Therefore it may be a promising new technology in diagnosing acute renal graft rejection after renal transplantation.
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Objective To investigate the effects of continuous venovenous hemodiafiltration (CVVHDF) on plasma lipopolysaccharide (LPS),interleukin(IL) 1β,IL-4,high mobility group box 1 (HMGB-1) in multiple organ dysfunction syndrome (MODS) dogs,to explore the therapeutic mechnism of CVVHDF.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=6) and MODS group (n=6).After endotoxin injection completed,the CVVHDF group received CVVHDF treatment for 24 h; MODS group did not receive CVVHDF treatment.The LPS,IL-1β,IL-4,HMGB-1 levels in plasma and ultrafiltrate were measured at different time points(before operation,before intravenous infusion of endotoxin,0 h,3 h,6 h,9 h,12 h,18 h,24 h after intravenous infusion completion of endotoxin),then the sieving coefficient (SC) was calculated.Results Compared with MODS group,the LPS,IL-1β,IL-4,HMGB-1 levels in plasma were significantly decreased in the CVVHDF group at 9 h,12 h,18 h,24 h (P ＜ 0.05).Some concentration of IL-1β,IL-4 and HMGB-1 was detected in the ultrafiltrate,the SC for IL-1β,IL-4 and HMGB-1 was 0.60±0.12,0.83±0.11,0.70±0.09 respectively,and LPS could not be detected in the ultrafiltrate,its SC was 0.After treatment,the damage level of lung and renal had been significantly reduced in CVVHDF group.Conclusion CVVHDF can effectively reduce the levels of pro-inflammatory mediator and anti-inflammatory cytokine related to MODS,cut off the vicious circle of cytokine network and reduce the damage level of organism in the treatment of MODS.