乳化氟碳结合川芎嗪对肝肺综合征猪肝移植围手术期肺部炎症的影响及其机制研究

Perfluorocarbon in combination with ligustrazine protects against lung injury during liver transplantation in pigs with hepatopulmonary syndrome

目的:探讨乳化氟碳结合川芎嗪对肝肺综合征(HPS)猪肝移植围手术期肺部炎症的影响及其机制。方法:采用慢性胆管结扎复制猪肝肺综合征模型,随机分为2组:(1)乳化氟碳结合川芎嗪(PFCL)组:肺内灌以20mL/kg的全氟碳乳剂(PFC)及川芎嗪(20mg/kg,气管内滴注),机械通气下进行原位肝移植;(2)机械通气对照(MV)组:常规MV下,进行原位肝移植。实验观察5h,实验结束后处死动物,取肺脏进行分析。结果:PFCL组肺脏的湿/干比值、肺通透指数及支气管肺泡灌洗液中白细胞计数均显著降低,与MV组比较差异显著(P<0.05);PFCL组肺组织及支气管肺泡灌洗液中肿瘤坏死因子α(TNF-α)、干扰素(IFN)-γ含量均显著低于MV组(P<0.05)。免疫组化染色发现,PFCL组肺组织炎症和上皮细胞核内NF-κBp65的含量明显低于MV组。结论:乳化氟碳结合中药川芎嗪可以有效地减少中性粒细胞浸润,抑制炎性细胞NF-κB的活化和细胞因子TNF-α与IFN-γ的表达,减轻HPS引起的肺损伤。

AIM ： To investigate the effects of perfluorocarbon and ligustrazine on lung injury during liver transplantation in pigs with hepatopulmonary syndrome. METHODS ： A hepatopulmonary syndrome （HPS） model of pig was established by chronic bile duct ligation. The animals were assigned randomly to 2 groups ： （ 1 ） Perfluorocarbon in combination with ligustrazine treatment groups （ PFCL group） ： the pigs were treated with intratracheal instillation of perfluorocarban and ligustrazine; （2） The conventional mechanical ventilation group （MV group） ： all animals were subjected to mechanical ventilation and orthotopic liver transplantation. After 5 h the lungs were harvested for further analysis. RESULTS： The lung wet to dry weight radio, puhnonary permeation index and leukocyte count in bronchoalveolar lavage fluids （BALF） in PFCL group significantly decreased compared to MV group （ P 〈 0. 05 ）. Contents of tumor necrosis factor- α （TNF -α） and interferon-γ（IFN -γ） in the lung tissue, plasma and BALF of pigs in PFCL group were significantly lower than those in MV group （P 〈 0. 05）. Moreover, the activation of NF -κB was inhibited markedly by PFCL. CONCLUSION： Perfluorocarbon in combination with ligustrazine effectively reduces the PMN accumulation in the lungs, inhibits TNF -or and IFN -γproduction and protects against lung injury during liver transplantation in pigs with hepatopulmonary syndrome.