N-去硫酸基团非抗凝肝素治疗脓毒症诱发急性肺损伤

N-desulfurized non-anticoagulant heparin in the treatment for acute lung injury induced by sepsis: An experimental study

目的 应用N-去硫酸基因非抗凝肝素治疗幼猪急性肠穿孔脓毒血症、ALI模型,为临床探索新的治疗途径。方法 健康幼猪17只随机分为对照组;模型组:切开盲肠,24h后关闭穿孔;治疗组:肠穿孔模型同前,ALI出现后,除机械通气基础治疗外,静脉注射12mg/kgN-去硫酸基因非抗凝肝素。每2h检测动脉血气、肺功能、血流动力学,并测定支气管肺泡灌洗液白细胞含量、病理及细菌学检查。结果 模型组ALI后Rrs进行性升高,PaO_2/FiO_2、Cdyn持续下降;血白细胞先升后降,而支气管肺泡灌洗液白细胞含量明显升高;肺泡和间质水肿、充血、出血、炎细胞浸润,肺泡扩张不均;血培养及腹腔液培养为大肠杆菌。治疗组应用N-去硫酸基因非抗凝肝素后PaO_2/FiO_2、Cdyn下降不明显,支气管肺泡灌洗液白细胞含量明显低于模型组;肺病理改变减轻。结论 N-去硫酸基因非抗凝肝素对脓毒症诱发的ALI具有一定治疗作用,其治疗机制可能是通过抑制肺内白细胞聚集、活化,使其向外周血释放。

Objective To study the effects of N-desulfurized non-anticoagulant heparin on the treat- ment of acute lung injury (ALI) induced by abdominal sepsis in piglets. Methods Seventeen piglets were randomly allocated to three groups namely: Group A(n = 5), animals underwent laparotomy without other interference as controls; Group B(n = 6), a perforation 2 cm in length was made in the distal cecum and re- paired 24 hours postoperatively; and Group C(n = 6), all procedures were made similar to group B, except heparin derivatives infused in the early stage of ALI. The hemodynamics, blood routine, blood gas and pul- monary function were recorded. The blood and peritoneal effusion were cultured. The bronchial-alveolar lavage fluid (BALF) was examined for neutrophil counts, bacterial culture and histologic examination. Re- sults Animals in group B showed ALI with PaO_2/FiO_2( < 300 mmHg) and Cdyn (compliance dynamics <30 % ) decreasing and respiratory resistance (Rrs) increasing ( > 40 % ). Blood neutrophil count in group B increased initially and decreased 8 h after the onset of ALI. Compared with Group B, group C had higher PaO_2/FiO_2 and lower Rrs at 8 h (P < 0.05). Blood neutrophil count in group C increased continually throughout the study and neutrophil count in BALF was lower than that in group B. At the same time, his- tological injuries in group C were mild than group B. Blood and peritoneal fluid bacterial culture were all positive after intervenient operation. Conclusion N-desulfurized non-anticoagulant heparin could alleviate lung injury in septic models by attenuating neutrophil infiltration and activation in the lung without any se- vere side effects.