双丁酰cAMP对大鼠烟雾吸入性肺损伤的防治作用  

Study on the Prophylactic Effects of Dibutyryl cAMP on Pulmonary Smoke Inhalation Injury in Rats

作　　者：李晓辉[1] 杨宗诚[2] 黎鳌[2] 

机构地区：[1]第三军医大学药理学教研室,重庆400038 [2]第三军医大学烧伤研究所,重庆400038

出　　处：《中国药科大学学报》2001年第6期432-435,共4页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助重大项目 ( 392 90 70 0 )

摘　　要：目的 :探讨细胞内第二信使分子 c AMP稳定的人工合成同系物双丁酰 c AMP对大鼠烟雾吸入性肺损伤的防治作用。方法 :分别采用干湿重法、伊文思兰荧光法、放射免疫分析法、过氧化氢还原法、TBA比色法测定肺组织含水量、肺微血管通透性 ( PMVP)、肺组织 c AMP水平、髓过氧化物酶 ( MPO)活性及脂质过氧化物MDA含量。结果 :大鼠吸入烟雾损伤后 2 h PMVP明显增大 ,6 h达高峰 ;同时肺含水量、MPO活性及 MDA含量显著升高 ,并出现呼吸衰竭的临床表现。与此相对应 ,肺组织 c AMP水平进行性下降 ,在时相上与 PMVP呈反相变化。双丁酰 c AMP( Db-c AMP)于伤后立即 ip能显著降低 PMVP、肺含水量 ,减少肺组织的白细胞浸润 ,减轻脂质过氧化损害 ,且呈剂量依赖性 ;能升高细胞内 c AMP的药物异丙肾上腺素 ( Iso)于伤后立即 ip,也具有类似作用。结论 :Db-c AMP对大鼠烟雾吸入性肺损伤具有防治作用 ,其机制与其减少肺组织白细胞浸润、减轻脂质过氧化损伤及降低吸入烟雾损伤大鼠 PMVP有关。AIM The purpose is to investigate the prophylactic effects of dibutyryl cAMP on the pulmonary smoke inhalation injury in rats. METHODS The water content of lungs, the pulmonary microvascular permeability(PMVP), the level of cAMP, the activity of myeloperoxidase(MPO), and the content of malondialdehyde (MDA) were determined with wet to dry weight ratio, evans blue fluorescence, radioimmunoassay, hydrogen peroxide reduction technique, and thiobarbituric acid spectrophotometry, respectively. RESULTS The PMVP was enlarged obviously at 2 h and reached the highest at 6 h post-smoke-inhalation injury in rats. The water content of lungs, the activity of myeloperoxidase(MPO) and the content of malondialdehyde (MDA) were increased greatly at the same time. Respiratory failure occurred. On the contrary, the level of cAMP was decreased progressively, which began at 2 h, and reached the lowerest at 6 h(P<0.01) post-smoke-inhalation injury in rats. Dibutyryl cAMP(Db-cAMP) ip inhibited the enlargement of PMVP and the increase of water content of lungs, reduced the leukocyte infiltration in injuried lung tissues, and alleviated peroxidation injury dose-dependently. Isoprenaline (Iso) ip had the similar effects. CONCLUSION Db-cAMP had prophylactic effects on the pulmonary injury post-smoke-inhalation in rats , the mechanisms of which were related to the decrease of leukocyte infiltration in injuried lungs ,the alleviation of peroxidation and the reduction of PMVP.

关 键 词：双丁酰环磷酸腺苷 肺微血管通透性 吸入性肺损伤 血气分析 动物实验 

分 类 号：R965[医药卫生—药理学] R974[医药卫生—药学]