【作者】 刘春雅；

【导师】 陈江华；

【作者基本信息】 浙江大学 ， 内科学， 2005， 硕士

【摘要】 引言 多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)是临床危重患者死亡的主要原因之一,目前临床上还缺乏有效的治疗手段。MODS的发病机制尚未完全阐明,目前研究认为,“炎症失控”假说能较为确切、合理地解释这一机制。炎症失控假说是由于机体受到创伤和感染刺激而产生炎症反应过于强烈,产生大量的促炎-抗炎介质,引起失控的炎症反应,使机体难以再维持内环境的稳定,最终导致SIRS(systemic inflammatory response syndrome)、MODS的发生,并引起死亡。目前连续性血液净化(continuous blood purification,CBP)不仅是一种传统的肾脏支持治疗手段,还作为免疫调节治疗手段在重症炎症中发挥重要作用,它能清除许多在SIRS/MODS中起作用的促炎及抗炎介质。针对MODS用CBP的方法清除炎症介质,进行免疫调节,已成为当前MODS防治研究的重点之一。目前研究认为连续性高容量血液滤过(continuous high volume hemofiltration,CHVHF)能有效清除在MODS发生过程中起作用的各类炎症介质,能提高动脉压更多还原

【Abstract】 IntroductionMODS is one of the major reason for the death of critical patients. In current, we have no effective therapy for MODS patients yet. The mechanism of MODS is keeping unclear, although the hypothesis of " overwhelming inflammation " has become the most popular one by now. When the body suffered from trauma or infection, a lot of pro-inflammatory and anti-inflammatory mediators would be produced, which often followed with overwhelming inflammation response and the disturbance of homeostasis. That would result in SIRS, MODS and finally death. Continuous renal replacement treatment (CRRT) is not only conceived as a replacement of the lost renal function, but also plays an important role in the therapy of serious inflammation asimmuno-modulator, by removing many soluble pro-inflammatory and anti-inflammatory mediators. By this reason, CRRT become a novel important treatment in SIRS/MODS. It has been accepted widely that continuous high volume hemofiltration (CHVHF) can remove these mediators more effectively than other hemofiltration . methods. However, the detail mechanism of CRRT in treatment of MODS and its influence on immune systems are still unclear. The purpose of this study was to investigate the influence of immune system of HVHF on MODS.Materials and methods1. Clinical data collectionA prospective study of 21 patients with MODS who underwent continuous high-volume hemofiltration between Nov.2004 and Apr.2005 was studied. The outcomes of the patients were recorded. 13healthy people served as control.2. Method of HVHFAll of the 21 patients underwent high volume veno-venous hemofiltration with a polysulfone filter (F60, 1.3 m2 ).The ultrafiltrate rate was 5000 ml/h and blood flow was 200~300 ml/min. The substitute fluid was infused with pumps pre and post filter.3. Detection of cytokines in serum and immune cell functionsPlasma levels of IL-1 ,IL-6,IL-10 and TNF-α were detected by ELISA assay. The antigen presenting function of whiteblood cells represented by HLA-DR expression was detected by flow cytometry analysis. T lymphocytes subsets (CD4, CD8 and CD4/CD8) were detected by immunofluorescence. Data from 13healthy people served as control.7.Statistical analysisFor statistical analysis, SPSS for windows vision 10.0 was used. A P value <0.05 was considered statistically significant.Results1. CHVHF was well tolerated in all the patients expect one gave up after 35 hours of CHVHF for other reasons. In these 21 patients, 12 patients survived through the 28 days’ observation period after CHVHF treatment (survive rate 57.1%), and finally 8 patients survived until now (survive rate 38.1%), in which 2 patients receiving hemodialysis therapy regularly.2.Compared with pre-treatment, serum levels of creatinine and urea were significantly decreased at the 24 hour of CHVHF (P<0.01).3.The serum levels of IL-1 and IL-6 were not significantly changed during CHVHF treatment in MODS patients4. A significant decrease of serum IL-10 was observed at the 12 hour of CHVHF treatment (P<0.05).5. Compared with pre-treatment, serum TNF-α levels weresignificantly decreased at the 6 hour of CHVHF (P<0.05), and very significantly decreased at the 12 hour (P<0.01).6.The expression of HLA-DR on white blood cells in MODS patients were significantly lower than that in healthy controls(P < 0.001).Compared with pre-CHVHF, HLA-DR levels were significantly improved at the 6 hour of CHVHF (P<0.05), and very significantly improved at the 12 hour (P<0.01).7.MODS patients had a significant lower CD4 level before HVHF than adult healthy controls (p < 0.001).There were no statistical difference of CD8 and CD4/CD8 ratio between MODS patients before HVHF and the controls (P=0.833 and 0.09 respectively). Compared with pre-HVHF, CD4 and CD4/CD8 levels were significantly increased at the 12 hour of HVHF (P=0.006 and 0.046 respectively).8. Serum levels of cytokine, CD4, CD8 and HLA-DR were not significantly changed during between death and survival in MODS patientsConclusions1.Compared with that before HVH更多还原