【摘要】 目的探讨高截留分子量膜行血浆透析滤过(PDF)对脓毒症状态下肾脏的保护作用。方法 20头清洁级国产公猪,日龄约80d,体重约36kg,采用盲肠结扎穿孔术制作脓毒症模型。术后24h,符合脓毒症诊断扩展标准的动物随机分入PDF组和连续性静脉-静脉血液滤过(CVVH)组,每天治疗8h。PDF组的膜材料为聚乙烯-乙烯醇的共聚体,截留相对分子质量为60 000~70 000,置换液为血浆与Port配方置换液以1比2为比例混合的液体,置换液流量为4mL·h-1·kg-1,透析液流量固定为1L/h。CVVH组的膜材料为聚砜膜,截留相对分子质量为20 000~30 000,血流量为2.5 mL·min-1·kg-1,前稀释法输入置换液40mL·h-1·kg-1。在造模前、入组即刻、入组4h、入组8h各时间点采用ELLSA检测血TNF-α三聚体、高迁移率组蛋白(HMGB1)水平。以动物肾的肌酐清除率较基础值降低75%为肾脏终点作生存分析。结果CVVH组的TNF-α三聚体浓度逐渐升高,PDF组的TNF-α三聚体浓度逐渐降低,应用广义估算方程模型分析,两组间差异有统计学意义(P=0.012)。与CVVH组相比,PDF组下调TNF-α三聚体浓度的OR值为1.97,95%CI为1.65~2.51。CVVH组的HMGB1浓度变化不明显,PDF组的HMGB1浓度随着治疗时间的延长逐渐降低,应用广义估算方程模型分析,两组间差异有统计学意义(P=0.007)。与CVVH组相比,PDF组下调HMGB1浓度的OR值为1.97,95%CI为1.67~2.46。PDF组有3例、CVVH组全部达到所设的肾脏事件终点。PDF组到达肾脏终点所需中位时间为31h,显著长于CVVH组的25h(P=0.005)。Cox回归发现,PDF组发生肾脏终点事件的危险是CVVH组的19.7%(P=0.029)。结论采用高截留分子量膜行PDF不仅能清除大分子炎性介质,还能降低大分子炎性介质的循环浓度,从而保护脓毒症动物的肾脏功能,延长了脓毒症动物的肾脏生存时间。更多还原

【Abstract】 Objective To explore whether plasma diafiltration(PDF)with high cut-off molecular weight membrane can improve the renal function in the state of sepsis.Methods Twenty domestic male swines,aged80 days,weighting about 36 kg,were used to made sepsis model by cecum ligation perforation(CLP).They were randomly divided into high cut-off molecular weight membrane group(group A)and common hemofilter membrane group(group B)24hafter CLP.The EVAL membrane of group A was made from polyethylene ethenol with60 000-70 000 molecular weight cut-off value,while the polysulfone membrane(F60)of group B with 20 000-30 000cut-off value.The swines in group A received 8hours of PDF every day.The hemofiltration solution consisted of plasma and substitution by Port formula in the ratio of 1to 2.The velocity of substitution was4mL·h-1·kg-1,and the dialysate flow was 1L/h.The swines in group B received 8-hour continuous venousvenous hemofiltration(CVVH)every day with 40 mL·h-1·kg-1 substitution and 2.5 mL·min-1·kg-1 blood flow.The concentrations of TNF-αand HMGB1 in blood were detected at 0,4,8hours from the start of blood purification.The end point of kidney survival analysis was the 75% decrease of creatinine clearance rate by baseline.Results The concentrations of TNF-αand HMGB1 in group A were significantly lower than those in group B(OR=1.97,95%CI:1.65-2.51,P=0.012;OR=1.97,95%CI:1.67-2.46,P=0.007).Three swines in group A and all the animals in group B reached the end point of kidney survival analysis.The median end point time in group A was significantly longer than that in group B(31hvs.25 h,P=0.005).The Cox regression showed that the kidney end point event risk of group A was 19.7% of group B(P=0.029).Conclusion The PDF with high cut-off molecular weight membrane can not only remove macromolecular plasma inflammatory mediators,but also reduce circulating concentration of the mediators.Thus it will protect kidney from the sepsis and increase renal survival time of sepsis animals.更多还原