双嘧达莫脂质体对小鼠油酸性急性肺损伤的保护作用

目的:考察双嘧达莫(dipyridamole,DIP)脂质体对小鼠油酸性急性肺损伤的保护作用.方法:小鼠随机分为7组:空白对照组、模型组、DIP注射液组、对照脂质体组和DIP脂质体低、中、高剂量组.给药15 min后,静注油酸致小鼠肺损伤.2 h后测定各组小鼠血清血管紧张素转换酶(SACE)、肺组织丙二醛(MDA)、超氧化物歧化酶(SOD)、支气管肺泡灌洗液(BALF)总蛋白含量、肺系数和湿重/干重比,并作肺组织病理切片.结果:模型组所有指标均较空白对照组有极显著性改变(P＜0.001),病理损伤明显;对照脂质体组各指标与模型组相比均无显著性差异(P＞0.05);DIP注射液组仅肺系数值比模型组有显著性降低(P＜0.05),病理损伤无明显改善;DIP脂质体中、高剂量组与模型组相比,BALF总蛋白含量、肺系数、湿重/干重比、SACE和肺组织MDA有极显著性降低(P＜0.01,P＜0.001),而肺组织SOD则有显著性升高(P＜0.05),病理切片显示肺损伤程度有显著改善;低剂量组仅SACE和肺系数有显著性降低(P＜0.05),病理损伤无明显改善.DIP脂质体与等剂量DIP注射液相比,BALF总蛋白含量、肺系数、湿重/干重比、SACE和肺组织MDA显著性降低(P＜0.05),而肺组织SOD则有显著性升高(P＜0.05).结论:DIP脂质体可以明显减轻小鼠油酸性急性肺损伤.其机制可能与脂质体保持DIP原型靶向于肺部,缓解脂质过氧化反应,保护肺血管内皮细胞有关.

Protection of Dipyridamole Liposomes against Acute Lung Injury Induced by Oleic Acid in Mice

AIM: To evaluate the protective effect of pulmonary targeting dipyridamole (DIP) liposomes on acute lung injury (ALI) in mice.METHOD:Mice were randomly divided into 7 groups,i.e.,oleic acid-induced,model,control liposomes,DIP injection,and three liposomes groups containing DIP of low,middle,and high doses.Except the first two groups,the rest of the groups were pretreated by intravenous administration of control liposomes,DIP injection and DIP liposomes of low,middle and high dose,respectively,15 min before the establishment of ALI model by intravenous injection of oleic acid 2 h later,the serum angiotensin converting enzyme(SACE),lung tissue (MDA),(SOD),(BALF protein content),lung index,wet/dry weight ratio were assayed,and pathomorphological changes in the lung were HE stained slices.RESULT: There were significant differences (P<0.001) between the model group and the control group in all of the above-mentioned observations.The model group showed obvious pathologic damages in the lung.There were no obvious difference (P>0.05) in each index between the model and control liposomes groups.While only lung index was significantly reduced in DIP injection group compared with the model group(P<0.05),and there is no evident improvement in pathologic damages in the former group.Comparing with the model group,SACE,lung tissue MDA, BALF protein content,lung index,wet/dry weight ratio were all significantly reduced in DIP liposomes groups of middle and high doses(P<0.01,P<0.001),while SOD significantly increased(P<0.05) and slices indicated pathologic damages were significantly ameliorated.Compared with the model group,only SACE and lung index were significantly reduced(P<0.05)in DIP liposome group of low dose,and no notable amelioration of pathologic damages was found.Comparing groups treated with DIP liposomes and injection of the same dose, BALF protein content,pulmonary index,wet/dry weight ratio,SACE,lung tissue MDA were all significantly decreased(P<0.05),while SOD significantly increased in former((P<0.05).)CONCLUSION:DIP liposomes had valid alleviating effect on ALI induced by oleic acid in mice.The mechanism might be attributed to the pulmonary targeting effect of DIP liposomes and its entrapment of DIP as its archetype,which has better suppression effect of lipid peroxidation reaction and the protection of pulmonary vascular endothelial cells than does DIP injection.