N-去硫酸基团肝素与低分子肝素对造模肠穿孔诱发急性肺损伤治疗作用的对比研究

Comparative study of N-desulfated heparin vs low molecular weight heparin in treating acute lung injury induced by sepsis

目的:在幼猪肠穿孔脓毒症诱发急性肺损伤(ALI)的动物模型基础上,比较N-去硫酸基团肝素与低分子肝素的治疗效果。方法:23只雄性幼猪随机分为:A组为假手术对照组(n=5),B组为模型组(n=6),C组为N-去硫酸基团肝素治疗组(n=6)及D组为低分子肝素治疗组(n=6)。于建立肠穿孔脓毒症诱发急性肺损伤模型后,在机械通气基础上,即刻在C组予静脉注射N-去硫酸基团肝素12mg/kg,D组予静脉注射低分子肝素抗Xa因子300IU/kg,观察比较动脉血气、肺动态顺应性、呼吸系统阻力、血流动力学、肺干湿重比、病理组织检查。结果:C组PaO2/FiO2、肺干湿重比相对较B组明显改善,呼吸系统阻力下降,肺动态顺应性下降不明显,肺组织病变减轻。D组仅肺干湿重比减轻,其他指标未见明显好转。结论:N-去硫酸基团肝素对肠穿孔脓毒症诱发的急性肺损伤有一定治疗作用,相对于低分子肝素在采用实验剂量下的治疗作用不明显。

Objectives To compare the therapeutic efficacy of N-desulfated heparin and low molecular weight heparin （LMWH） in treating acute lung injury （ALI） induced by sepsis. Methods A total of 23 male piglets were randomly allocated into the following 4 groups： group A （n=5）, sham operation; group B （n=6）, septic models without treatment; group C （n=6）, septic models receiving N-desulfated heparin treatment （12 mg/kg）, and group D （n=6）, septic models receiving LMWH treatment （anti-Xa 300 IU/kg）. The blood gas, parameters of hemodynamics, as well as the pulmonary functions were monitored; lung wet/dry ratio （W/D） and histopathological changes in each group were compared. Results Compared with those in group B, PaO2/FiO2 and compliance dynamic （Cdyn） were improved in group C, meanwhile the W/D and resistance of respiratory system （Rrs） were decreased; the morphologic injuries in group C were milder. No significant improvement of PaO2/FiO2 and pulmonary functions were found in group D, compared with those in group C, except that W/D was decreased. Conclusions N-desulfated heparin can attenuate lung injuries in the ALI model induced by sepsis. This agent is more effective than LMWH in the treatment of ALI.