低剂量低分子肝素对内毒素诱发的急性肺损伤的影响

Effects of low-dose low molecular weight heparin on lipopolysaccharide-induced acute lung injury

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6mg/kg LPS诱发ALI。C组腹腔注射低分子肝素100U/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 interleukinlβ（IL-1β） ,IL-6 and tumor necrosis faetor-α（TNF-α） were de- termined 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.