血浆透析滤过改善脓毒症急性肾损伤的动物实验  

Effect of plasma diafiltration on acute kidney injury in sepsis animal model

作　　者：鲁鉴达 李铭新[1] 刘骏峰[1] 汪伟[2] 孙鹏[3] 项建斌[3] 薛骏[1] 顾勇[1] 郝传明[1] 林善锬[1] 

机构地区：[1]复旦大学附属华山医院肾脏科,上海200040 [2]复旦大学附属华山医院重症医学科,上海200040 [3]复旦大学附属华山医院普外科,上海200040

出　　处：《上海医学》2015年第5期415-420,I0001,共7页Shanghai Medical Journal

基　　金：国家自然科学基金资助项目(81271731)

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。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, aged 80 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） 24 h after CLP. The EVAL membrane of group A was made from polyethylene ethenol with 60 000-70 000 molecular weight cut-off value, while the polysulfone membrane （F60） of group B with 20 000- 30 000 cut-off value. The swines in group A received 8 hours of PDF every day. The hemofiltration solution consisted of plasma and substitution by Port formula in the ratio of 1 to 2. The velocity of substitution was 4 mL·h^-1·kg^-1, and the dialysate flow was 1 L/h. The swines in group B received 8-hour continuous venous- venous 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-α and HMGB1 in blood were detected at 0, 4, 8 hours 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-a and HMGB1 in group A were significantly lower than those in groupB （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 （31 h vs. 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

关 键 词：腹腔镜 盲肠结扎穿孔 脓毒症 血浆透析滤过 

分 类 号：R692[医药卫生—泌尿科学]