血浆透析滤过改善脓毒症急性肾损伤的动物实验

发布时间：2018-06-16 02:51

本文选题：腹腔镜 + 盲肠结扎穿孔　；参考：《上海医学》2015年05期

【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。
[Abstract]:Objective to investigate the protective effect of plasma dialysis filtration (PDF) with high retention molecular weight membrane (HMWM) on kidney in septic state. Methods 20 clean grade domestic boars, aged about 80 days and weighing about 36 kg, were used to establish sepsis model by cecal ligation and perforation. 24 hours after operation, animals that met the criteria for the diagnosis of sepsis were randomly divided into PDF group and continuous veno-venous hemofiltration (CVVH) group. The membrane materials of the 8h. PDF group were polyvinylenol copolymers. The retention molecular weight was 60000 / 70,000. The replacement solution was a mixture of plasma and Port formula replacement solution in the ratio of 1: 2, the flow rate of the replacement fluid was 4 mL h-1 kg-1, the flow rate of dialysis solution was fixed at 1L / h. CVVH group was polysulfone membrane. The retained molecular weight was 20 000 g / kg and the blood flow was 2.5 mL / kg ~ (-1). The replacement solution was injected with 40 mL / h ~ (-1) kg ~ (-1) by predilution method. Serum TNF- 伪 trimer and high mobility histone (HMGB1) levels were detected by ELLSA before, immediately, 4 hours and 8 hours after injection. A 75% decrease in creatinine clearance from the basic value of the kidney was used for the survival analysis of the renal endpoints. Results the concentration of TNF- 伪 trimer in CVVH group increased gradually, and the concentration of TNF- 伪 trimer in PDF group decreased gradually. The difference between the two groups was statistically significant by using the generalized estimation equation model. Compared with the CVVH group, the OR value of down-regulating TNF- 伪 trimer concentration in PDF group was 1.97 卤95CI = 1.65 卤2.51.The HMGB1 concentration in PDF group decreased gradually with the prolongation of treatment time. The difference between the two groups was statistically significant by using generalized estimation equation model. Compared with CVVH group, the OR value of down-regulating HMGB1 concentration in PDF group was 1.97 卤2.46. There were 3 cases of CVVH group that all reached the established renal event endpoint. The median time to reach renal endpoint in PDF group was 31 hours, which was significantly longer than that in CVVH group (25 h P0. 005. Cox regression). The risk of renal end-point events was 19. 7 and 0. 029 in CVVH group. Conclusion PDF can not only remove macromolecular inflammatory mediators, but also decrease the circulating concentration of macromolecular inflammatory mediators, thus protect the renal function of septic animals and prolong the kidney survival time of septic animals.
【作者单位】：复旦大学附属华山医院肾脏科;复旦大学附属华山医院重症医学科;复旦大学附属华山医院普外科;
【基金】：国家自然科学基金资助项目(81271731)
【分类号】：R692

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