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肾脏病与透析肾移植杂志 ›› 2013, Vol. 22 ›› Issue (4): 340-345.

• 论文 • 上一篇    下一篇

连续性静脉-静脉血液透析滤过防治犬多脏器功能障碍综合征

  

  • 出版日期:2013-08-28 发布日期:2013-09-03

Changes of LPS, CD14 and HMGB-1 in dogs with multiple organ dysfunction syndrome treated with continuous veno-venous haemodiafiltration

  • Online:2013-08-28 Published:2013-09-03

摘要:

摘要  目的  观察连续性血液透析滤过(CVVHDF)防治犬多器官功能障碍综合征(MODS)过程中内毒素(LPS)、内毒素受体(CD14)和高迁移率族蛋白1(HMGB-1)的变化。方法  18只雄性Beagle犬随机分为正常对照组(n=6)、MODS组组(n=6)和CVVHDF组(n=6)。采用失血性休克+复苏灌注+内毒素血症建立MODS模型[1], CVVHDF组在内毒素注射完毕后给于CVVHDF治疗24小时, MODS组不给CVVHDF治疗。术前(T1)、内毒素注射前(T2)、内毒素注射完毕后0h(T3)、3h(T4)、6h(T5)、9h(T6)、12h(T7)、18h(T8)及24h(T9)观察血浆LPS、CD14及HMGB-1变化,及各脏器组织CD14、HMGB-1蛋白表达和病理学改变。结果  经CVVHDF治疗后,CVVHDF组血浆LPS、CD14及HMGB-1水平均逐渐下降,在T6-9时间点显著低于MODS组(P<0.01)。CVVHDF组各组织中CD14、HMGB-1蛋白表达均有所降低,其中,CVVHDF组肝脏及脑组织CD14蛋白表达显著低于MODS组(P<0.05),CVVHDF组肺脏、肾脏及脑组织HMGB-1蛋白表达显著低于MODS组(P<0.05)。CVVHDF治疗后肺脏、心脏、肝脏、肾脏及脑组织病理损伤明显减轻。结论  过度的炎症反应是MODS发生的本质原因之一,CVVHDF能够削弱学循环中LPS、CD14及HMGB-1等炎症介质的峰值浓度,下调肺脏、心脏、肝脏、肾脏及脑组织中CD14、HMGB-1蛋白表达,有效遏制过度的炎症反应,从而起到防治MODS的作用。

关键词: 关键词 , 多器官功能障碍综合征, 血液透析滤过; , 内毒素;内毒素受体;高迁移率族蛋白1

Abstract:

Abstract  Objective: To observe the changes of endotoxin (LPS), its receptor CD14 and high mobility group-1 protein (HMGB1) in dogs with multiple organ dysfuncition syndrome (MODS) treated with continuous veno-venous haemodiafiltration (CVVHDF). Methodology:Eighteen male Beagle dogs were randomly divided into normal control group (n=6), MODS group (n=6) and HVH F group (n=6). Hemorrhagic shock plus resuscitation and endotoxemia (two-hit) method was used to establish the dog MODS model. CVVHDF was performed about 24 hours after LPS injection in MODS dogs of CVVHDF group. Plasma LPS, CD14 and HMGB-1 were determined before operation(T1), before LPS injection (T2) and 0h(T3), 3h(T4), 6h(T5), 9h(T6), 12h(T7), 18h(T8) and 24h(T9) after LPS injected. Protein express levels of CD14 and HMGB-1 in main organ tissues were detected by fluorescent detection of Western blot. Pathological changes of main organ tissues were observed under the light microscopy.  Results:  Compared with the MODS group, plasma levels of LPS, CD14 and HMGB-1 were significantly decreased in the CVVHDF group at T6-9 (P<0.01). In CVVHDF group, protein express levels of CD14 and HMGB-1 in main organ tissues were decreased. The CD14 protein express levels of liver and brain in CVVHDF groups were significantly lower than that in MODS group (P<0.05). The HMGB-1 protein express levels of lung, kidney and brain in CVVHDF groups were significantly lower than that in MODS group (P<0.05). Pathological changes of major organs were improved in the CVVHDF group, as compared with animals in the MODS group.  Conclusion: Excessive inflammatory response may be the essential pathogenesis of MODS. CVVHDF can cut down the peak value of inflammatory cytokines including LPS, CD14 and HMGB-1, down-regulate protein express levels of CD14 and HMGB-1 in main organ tissues, which can prevent and treat MODS.

Key words: Key words , multiple organ dysfuncition syndrome, hemodiafiltration, LPS;CD14;HMGB-1