卢帕他定对急性肺损伤的保护作用研究及对LPS诱导的大鼠巨噬细胞系NR8383的作用研究-微生物与生化药学专业论文.docxVIP

AbstractAcute Abstract Acute lung injury(AL0 and its more severe form，the acute respiratory distress synome(ARDS)，are syndromes of acute respiratory ffilllre that result from acute pulmonary edema and inflammation．The pathogenesis ofthem is complicated and not well known．They have hi曲mortality and no effective cure has been established． Rupatadine is a new agent for the management of disease with allergic inflammatory conditions，such as seasonal and perennial rhinitis。It is a potent dual antagonist of histamine and platelet-aetivating factor口AF)，possessing a unique profile as it combines both activities with a high level ofpotency．Them were no reports about its effect’011 lung inflammation．In the present study,we established the AM／ARDS animal models and investigated rupatadine’S protect effect and mechanisms．In addition,we studied the intervene effect of mpatadine on lipopolysaeeharide (LPS)一mediated inflammatory factors in pulmonary alveolar macrophage cell line NR8383． 1．The protective effect ofrupatadine on oleic acid-inducedALl in rabbits Rupatadine Was given intravenously through mfll_gill with a sustaining infusion 30rains before OA injection．The OA—induced descent of arterial blood oxygen pressure Was inhibited，as well as PAF，ICAM-1，IL-8 in bronchoalveolar lavage fluid (BALF)in rupatadine group，Furthermore，the changes in edema fluid accumulation in BLAF、wet／dry weight ratio、histopathology observation in the lung are all alleviated or attenuawxl by mpatadine administration． 2．Effect ofrupatadine onALl induced by oleic acid in rats Rupatadine Was given before injection of oMc acid at dose of 1 0，20，40mg／kg． The changes of lung inspiratory resistance，expiratory resistance and dynamic lung compliance were real time recorded by artrise2005 pdmonary function test apparatus． Lung wet to dry weight ratio was ealcmated．The concentration ofprotein and TNF’口 level in BALF were measured．Pretreatment of mpatadine significantly allevimed lung injury by improvement of lung