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目的:初步探讨配对血浆滤过吸附(CPFA)串联血液透析对多脏器功能障碍综合征(MODS)患者内皮细胞功能的影响。方法:选择MODS患者7例,均在常规治疗基础上加用CPFA串联血液透析(A)和高容量血液滤过(HVHF)(B)治疗,A,B治疗顺序随机,间隔一夜洗脱期(12h)。记录患者相关的临床情况并计算治疗前后APACHE II评分及最终人肾存活情况。分别在CPFA、HVHF治疗0、5、10h采集患者血浆,检测sE选择素、血栓调节蛋白(sTM)的浓度。另取不同治疗时间点患者血清与正常人脐静脉内皮细胞(HUVEC)共同孵育24h,检测上清液中sE选择素及sTM的浓度。结果:(1)两种治疗平均动脉压(MAP)均明显升高(99.00±18.02vs.120.75±20.02,92.33±18.33vs.115.33±18.50,P<0.05),且升压药剂量减少;CPFA后APACHE II评分有明显下降,差异有统计学意义(25.25±7.18vs.19.00±6.83,P<0.05);HVHF后APACHE II评分有下降趋势但差异无统计学意义(27.00±5.29vs.22.33±5.13,P>0.05);(2)患者体循环血清sE选择素、sTM浓度显著高于正常对照组(176.7±76.7vs.35.1±10.4,8.44±1.81vs.4.54±2.97,P<0.01);经过HVHF一个循环后E-选择及sTM水平略有下降(P>0.05),经过CPFA一个循环,这两种标志物的水平明显下降(179.1±77.4vs.161.3±74.3,8.42±1.90vs.6.83±1.39,P<0.05);HVHF或CPFA治疗后,患者体循环中血清sE选择素、sTM浓度有下降趋势,但均未达统计学意义(P>0.05);(3)HVHF治疗10h的血清刺激HUVEC,上清液中sTM水平明显下降(15.29±3.11vs.10.29±2.74,P<0.05),5h时上清液中sE选择素、sTM的浓度变化不明显(37.33±8.33vs.25.74±4.23,15.29±3.11vs.12.93±3.12,P>0.05);CPFA治疗5h的血清刺激HUVEC,上清液中sTM的水平已明显下降(15.01±2.99vs.11.41±2.72,P<0.05),到10h时上清液中sE选择素明显下降(37.99±8.75vs.21.64±3.12,P<0.05),sTM浓度下降更显著(15.01±2.99vs.9.32±3.21,P<0.01)。结论:MODS患者内皮细胞功能明显异常。CPFA较HVHF在一次循环中能更有效地清除sE选择素及sTM;体外实验表明相对于HVHF,CPFA能更早且更好的改善内皮细胞的功能。
Objective: To investigate the effect of paired plasma filtration adsorption (CPFA) tandem hemodialysis on endothelial cell function in patients with multiple organ dysfunction syndrome (MODS). Methods: Seven patients with MODS were selected. All of them were treated with CPFA tandem hemodialysis (A) and high-volume hemofiltration (B) after conventional treatment. The treatment sequence of A and B were randomly divided into one washout interval 12h). The patient’s clinical status was recorded and APACHE II scores and final human kidney survival were calculated before and after treatment. Plasma samples were collected at 0, 5 and 10 h after CPFA and HVHF treatment, respectively. The concentrations of sE-selectin and thrombomodulin (sTM) were measured. In addition, serum from different treatment groups was incubated with normal human umbilical vein endothelial cells (HUVECs) for 24h, and the concentrations of sE-selectin and sTM in the supernatant were measured. Results: (1) The mean arterial pressure (MAP) of both groups were significantly increased (99.00 ± 18.02 vs 120.75 ± 20.02, 92.33 ± 18.33 vs 115.33 ± 18.50, P <0.05) The APACHE II score decreased significantly after the HVHF (25.25 ± 7.18 vs.19.00 ± 6.83, P <0.05), but the difference was not statistically significant (27.00 ± 5.29 vs.22.33 ± 5.13, P> 0.05). (2) The serum sE-selectin and sTM concentrations in patients with systemic circulation were significantly higher than those in the normal control group (176.7 ± 76.7 vs 35.1 ± 10.4, 8.44 ± 1.81 vs 4.54 ± 2.97, P <0.01) After one cycle of HVHF, the levels of E-selectin and sTM decreased slightly (P> 0.05). After one cycle of CPFA, the levels of these two markers were significantly decreased (179.1 ± 77.4 vs 161.3 ± 74.3, 8.42 ± 1.90 vs.6.83 ± 1.39, P <0.05). After HVHF or CPFA treatment, the levels of serum sE-selectin and sTM in the systemic circulation decreased but did not reach statistical significance (P> 0.05). (3) Serum of HVHF-treated 10h stimulated HUVEC , The level of sTM in the supernatant decreased significantly (15.29 ± 3.11vs. 10.29 ± 2.74, P <0.05), and the concentration of sE-selectin and sTM in the supernatant did not change significantly at 5h (37.33 ± 8.33vs.25.74 ± 4.23, 15.29 ± 3.11 vs. 12.93 ± 3.12, (P <0.05). The level of sTM in the supernatant of the HUVEC stimulated by CPFA for 5 h was significantly decreased (15.01 ± 2.99 vs.11.41 ± 2.72, P <0.05), and the level of sE-selectin in the supernatant decreased significantly (37.99 ± 8.75vs.21.64 ± 3.12, P <0.05). The sTM concentration decreased more significantly (15.01 ± 2.99 vs.9.32 ± 3.21, P <0.01). Conclusion: The function of endothelial cells in patients with MODS is obviously abnormal. CPFA cleaves sE-selectin and sTM more efficiently than HVHF in one cycle; in vitro experiments show that CPFA improves endothelial cell function earlier and better than HVHF.