亲和吸附材料特异性清除外源性内毒素有效性的研究

摘要

Objective To investigate the effectiveness of the affinity adsorption material developed by our team for the specific removal of exogenous endotoxin in the blood circulation. Methods Fifteen beagle dogs were intravenously injected with endotoxin to establish a dog model of endotoxemia, and then they were randomly divided into the treatment group(n=10)and the control group(n=5). The treatment group received an extracorporeal perfusion to remove the endotoxin using the self-made disposable hemoperfusion device,while the control group using routine perfusion device. The levels of endotoxin, tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), interleukin 6(IL-6)and interleukin 8 (IL-8)in the blood of the dogs were measured at the beginning and 120 min after hemoperfusion for 120 minutes. The vital signs of the dogs were monitored during the hemoperfusion. Results After successful establishment of the endotoxemia model,the level of endotoxin at the beginning of hemoperfusion in the treatment group and control group was 118.63 ± 27.98 EU/mL and 117.16 ± 22.95 EU/mL,respectively. After hemoperfusion for 120 min,it was 0.039 ± 0.01 EU/mL and 131.98 ± 7.01 EU/mL, showing a significant difference(P﹤0.05). The clearance rate of hemoperfusion in the treatment group was 94.07%. At the beginning of hemoperfusion, the levels of TNF-α, IL-1β, IL-6 and IL-8 in the treatment group were 1.53 ± 0.27 ng/mL,12.82 ± 1.66 ng/mL,54.77 ± 3.98 ng/mL and 0.25 ± 0.32 ng/mL, and the levels in the control group were 1.53 ± 0.06 ng/mL,13.05 ± 0.18 ng/mL,54.58 ± 0.19 ng/mL and 0.28 ± 0.06 ng/mL, respectively. After hemoperfusion for 120 min, the levels of TNF-α, IL-1β, IL-6 and IL-8 in the treatment group were 0.13 ± 0.06 ng/mL, 0.70 ± 0.36 ng/mL, 1.62 ± 0.80 ng/mL and 0.01 ± 0.00 ng/mL, respectively, and as for the control group,the levels were 2.26 ± 0.15 ng/mL,15.12 ± 0.18 ng/mL,62.54 ± 0.93 ng/mL and 0.73 ± 0.93 ng/mL. There were significant differences between the beginning and after perfusion for 120 min in those two groups(P< 0.05). Conclusions This affinity adsorption material can effectively remove endotoxin and the inflammatory mediators in the blood of experimental dogs,with a clearance rate of 94.07%.%目的 研究本课题组研发的亲和吸附材料特异清除外源性内毒素的有效性.方法 15只比格犬静脉输注内毒素制造内毒素血症模型后随机分为治疗组(n=10)和对照组(n=5),治疗组用本课题组研发的一次性血液灌流器进行干预,对照组不用该灌流器.在灌流开始、120 min测定犬血液中内毒素及肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)、白介素6(IL-6)、白介素8(IL-8)的水平;灌流过程中监测犬的生命体征.结果 造模成功后,治疗组、对照组灌流开始血液中内毒素水平分别为(118.63 ± 27.98)、(117.16 ± 22.95)EU/mL,灌流120 min分别为(0.039 ± 0.01)、(131.98 ± 7.01)EU/mL,治疗组灌流后内毒素清除率达94.07%.灌流开始治疗组血液中TNF-α、IL-1β、IL-6、IL-8水平分别为(1.53 ± 0.27)、(12.82 ± 1.66)、(54.77 ± 3.98)、(0.25 ± 0.32)ng/mL,对照组分别为(1.53 ± 0.06)、(13.05 ± 0.18)、(54.58 ± 0.19)、(0.28 ± 0.06)ng/mL;灌流后120 min 治疗组血液中TNF-α、IL-1β、IL-6、IL-8水平分别为(0.13 ± 0.06)、(0.70 ± 0.36)、(1.62 ± 0.80)、(0.01 ± 0.00)ng/mL,对照组分别为(2.26 ± 0.15)、(15.12 ± 0.18)、(62.54 ± 0.93)、(0.73 ± 0.93)ng/mL,两组灌流开始与120 min各指标分别相比,差异有显著性(P< 0.05).结论 该亲和吸附材料能有效清除实验犬血液中的内毒素及炎症介质,清除率达94.07%.