低剂量低分子肝素对内毒素诱发的急性肺损伤的影响

摘要

目的 探讨低剂量低分子肝素(LMWH)对内毒素(LPS)诱发的急性肺损伤(ALI)的影响.方法 选取36只雄性SD大鼠分为3组:正常对照组(A组),LPS组(B组)和LPS+ LMWH组(C组),每组12只.B、C组腹腔注射6 mg/kg LPS诱发ALI.C组腹腔注射低分子肝素100 U/kg,B组腹腔注入同等容积的生理盐水.6h后处死动物,光镜下观察各组大鼠肺组织病理改变,行动脉血气分析、检测肺湿质量/干质量(W/D)比值和支气管肺泡灌洗液(BALF)中总蛋白浓度;测定肺组织髓过氧化物酶(MPO)活性、丙二醛(MDA)水平;ELISA法测定血浆中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)及白细胞介素6(IL-6)水平.结果 B、C组PaO2、pH值低于A组,C组与B组相比明显升高(P＜0.05).B、C组大鼠肺W/D、BALF总蛋白及肺组织MDA、MPO水平明显高于A组(P＜0.01);C组与B组相比,肺W/D、BALF中蛋白及肺组织MDA、MPO水平明显下降(P＜0.05).B、C组大鼠血浆中TNF-α、IL-1β及IL-6水平较A组明显升高(P＜0.01),而C组较B组明显降低(P＜0.01).结论 LMWH处理能够减轻LPS诱发的急性肺损伤.%Objective To explore the effect of low-dose low molecular weight heparin(LMWH) on acute lung injury(ALI) induced by lipopolysaccharide(LPS).Methods Thirty-six male SD rats were divided into 3 groups:normal control group(A),LPS group(B) and LPS plus LMWH group(C),12 cases in each group.ALI was induced by intraperitoneal injection of LPS 6 mg/kg in group B,C.The group C accepted intraperitoneal injection of LMWH 100 U/kg,the groups B accepted intraperitoneal injection of the same volume of normal saline.The animals were killed after 6 h,the pathological changes of the lung were observed under light microscope.Arterial blood gases,lung wet to dry ratio (W/D) and protein content in BALF were detected;the levels of MPO and MDA in lung tissue were determined.The levels of serum interleukin1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α) were determined by ELISA method.Results The PaO2 and pH values in the group B and C were significantly lower than those in the group A,and which in the group C were markedly increased compared with those in the group B(P＜0.05);the lung W/D ratio,protein content in BALF,MDA and MPO levels in the lung tissue in the group B and C were significantly higher than those in the group A(P＜0.01),while the lung W/D ratio,protein content in BALF,MDA and MPO levels in the lung tissue in the group C were significantly decreased compared with the group B (P＜0.05).The levels of plasma TNF-α,IL-1β and IL-6 levels in the group B and C were markedly increased compared with the group A,while which in the group C were significantly decreased compared with those in the group B (P＜0.01).Conclusion The LMWH treatment might attenuate LPS-induced acute lung injury.