QNB对抗全氟异丁烯吸入急性肺损伤的防治作用

The Role of QNB against Acute Lung Injury induced by PFIB Inhalation

目的评价二苯羟乙酸-3-喹咛环酯(3-quinuclidinylbenzilate,QNB)对全氟异丁烯(Perfluoroisobutylene,PFIB)吸入急性肺损伤的防治效果,并初步探讨其血液流变学作用机制。方法以小鼠全身暴露动态吸入染毒方式造成PFIB吸入肺损伤模型,QNB给药剂量5mg/kg,i.p.。预防组染毒前30min给药,治疗组染毒后10h给药,以染毒后24h肺系数(湿肺/体比,干肺/体比,肺湿/干比),支气管肺泡灌洗液(Bronchoalveolarlaragefluid,BALF)中总蛋白含量,以及72h存活率,评价QNB防治效果。以头部暴露动态吸入方式染毒大鼠,测定染毒后2,8,16h外周血液流变学变化,观察QNB5mg/kg的预防作用。结果QNB5mg/kg预防和治疗可显著降低各项肺系数,显著改善肺内蛋白漏出,提高存活率。PFIB吸入后可引起外周白细胞减少,红细胞聚集指数和全血粘度增加,血浆粘度和红细胞压积无显著改变。QNB5mg/kg预防可部分对抗PFIB引起的血液流变学改变。结论QNB对PFIB吸入肺损伤具有预防和治疗作用,可能与改善微循环有关。

Objective To investigate the role of 3-quinuclidinyl benzilate （QNB） on acute lung injury （ALl） induced by PFIB inhalation, and to unveil the mechanism of hemorheological changes. Method Mice were exposed to PFIB in a flow-past chamber, and administrated with QNB （5mg/kg,i. p. ） prophylactically （30min before exposure） or therapeutically （10h after exposure）. Lung index （wet lung/body weight, the dry lung/body weight, and lung wet/dry weight ratios）,the total protein concentration in bronchoalveolar lavage fluid（BALF） at 24h and mortality at 72h after exposure were determined. The time course of rats peripheral blood, hemorheology changes after exposure was also observed. Results It was found that the increasing Lung index, total protein concentration in BALF, and mortality, which triggered by PFIB inhalation, were partly blocked by QNB administration. Hemorheology assay showed blood viscosity at shear rate of 1s^-1 and erythrocyte aggregation were significantly raised in rats since 8h post PFIB exposure,while hematocrit and plasma viscosity were not altered significantly. Leukopenia was quickly appeared since 2h after PFIB inhalation. Beneficial effects of QNB （5mg/kg i. p. ）pretreatment at 30min before exposure were exerted by decreasing blood viscosity, erythrocyte aggregation and leucocyte counts. Conclusion QNB administration can play prophylactic or therapeutic roles in ALI induced by PFIB inhalation, which may involved in ameliorating pulmonary microcirculation.