高容量血液滤过对猪胰腺炎模型细胞因子水平的影响

Effects of high volume hemofiltration on plasma cytokines in pigs with severe acute pancreatitis

目的:研究高容量血液滤过(HVHF)对重症急性胰腺炎(SAP)动物生命特征和血浆细胞因子水平及单核细胞分泌功能的影响。方法:在100mmHg压力下自主胰管逆行按1ml/kg缓慢注入4%牛黄胆酸钠溶液诱导模型产生。胰腺炎模型建立后,实验动物被随机分为三组。组1(n=8)为对照组,组2(n=8)为连续性静脉-静脉血液滤过(CVVH)治疗组[20ml/(kg.h)],组3(n=8)为高容量血液滤过(HVHF)治疗组[100ml/(kg.h)]。治疗中采用Swans-Ganz导管监测血流动力学指标,并用ELISA方法检测血浆细胞因子水平,分离单核细胞后经培养用脂蛋白刺激后检测单核细胞分泌功能。结果:治疗组动物存活时间明显长于对照组,HVHF组更明显。HVHF治疗后,心率(HR)、平均动脉压(MAP)、外周血管阻力(SVRI)等指标均可改善。同时HVHF组的血浆细胞因子水平如白介素6(IL-6),肿瘤坏死因子α(TNF-α)和IL-10明显降低(P<0.01)。在胰腺炎早期,HVHF组动物过度活化的单核细胞分泌功能,包括分泌IL-6,TNF-α和IL-10的功能均明显受到抑制(P<0.05),36h后,对照组动物单核细胞分泌TNF-α、IL-6的活性进入过度抑制状态,而HVHF组单核细胞分泌功能则得到改善(P<0.05),在IL-10分泌活性方面,36h后,对照组活性仍持续高于正常水平,而HVHF组持续受到抑制。结论:SAP在病理生理过程中主要表现为系统性炎症反应。HVHF可以降低细胞因子水平,改善单核细胞分泌功能,重建免疫平衡,从而改善脏器损伤及预后。HVHF明显优于传统剂量的CVVH。

Objective ：To observe the role of hemofiltration on pacreatitis, and to investigate the effects of different hemofiltration intensity on general conditions, plasma cytokines, and monocyte function in pigs with severe acute pancreatitis （SAP）. Methodology：Pancreatitis was induced by pressure-controlled （ 100 mmHg） , intraductal injection of sodium taurocholate （4% , 1 ml/kg）. After inducement 24 pigs were randomly divided into three groups. Group Ⅰ （n = 8） served as SAP controls received only saline, group Ⅱ （ n = 8 ） accepted a low volume [ 20 ml/（ kg· h ] continuous veno-venous hemofiltration （CVVH） and group m 〈 n=8） received high volume hemofiltration （HVHF） [100 ml/（kg.h） ] at the same time of the inducement of SAP. The machine of EQUA-smart （ Medica, Italy） was used in this study. Zero-balanced hemofiltration was performed with a blood flow rate of 80 ml/min in a pre-dilution mode using AN69 （ polyacrylonitrile, 1.2 m^2 , Hospal, France）. The filters were replaced daily. The heparin was used to avoid coagulation. The serum concentrations of cytokines were measured using specific enzyme-linked immunosorbent assays （ELISA）. The monocytes were separated and stimulated by LPS to detect cytokines production. Results：Survival time was significantly prolonged both by low-volume CVVH and HVHF, which was more prolongation in the latter （P 〈 0. 05）. The major hemodynamic finding, such as pancreatitis-induced hypotention, was significantly attenuated by HVHF （P 〈 0. 05 ）. The development of hyperdynamic circulatory failure was simultaneously attenuated （ P 〈 0. 05 ）, as reflected by an attenuated decrease in systemic vascular resistance （P 〈0.05 ）. The serum concentrations of cytokines such as IL-6, TNF-a and IL-10 decreased significantly in hemo- filtration groups （ P 〈 0.01 ）, especially in HVHF group （ P 〈 0.05 ）. In the early stage of SAP, there was a significant reduction of TNF-α, IL-6 and IL-10 secreted by monocytes in the hemofiltration groups （ P 〈 0.05 ）. But at 36 h after the induction of SAP, the activities of TNF-α and IL-6 secreted by monocytes in hemofiltration groups were higher than in controls （ P 〈 0.05 ）, while the activity of IL-10 in hemofiltraion groups were lower than in controls. Conclusion： Our data suggested that HVHF was distinctly superior in preventing pancreatitis-related hemodynamic impairment and immune disorders compared with low-volume CVVH, which might contribute to the improvement of the hyperdynamic circulatory failure and excess inflammatory response.