别嘌呤醇对大鼠吸入性肺损伤的作用及其机制探讨

本实验采用大鼠烟雾吸入模型,观察了预先给予别嘌呤醇对吸入性肺损伤后6h内肺微血管通透性、丙二醛生成、超氧化物歧化酶活性、肺灌洗液中蛋白浓度及白细胞计数和血清丙二醛的影响,并辅以肺脏病理检查。结果表明:别嘌呤醇对吸入伤大鼠可以显著降低肺微血管通透性,减少肺灌洗液中蛋白含量及白细胞计数,组织病理学检查也可见肺充血、出血、间质和肺泡水肿减轻,白细胞浸润减少等。别嘌呤醇在减轻肺水肿的同时,也使肺及血清丙二醛水平明显降低,而肺组织丙二醛含量的变化在伤后6h内与肺微血管通透性、肺灌洗液中蛋白含量及白细胞计数的变化在时间及程度上都一致。以上结果提示,别嘌呤醇通过抑制黄嘌呤氧化酶,减少超氧阴离子产生,从而抑制肺脂质过氧化,减轻吸入性肺损伤。

Effects of Allopurinol on Inhalation Pulmonary Injury in Rats

Six hours after inhalation pulmonary injury,the pulmonary microvascular permeability (PMVP),pulmonary malondialdehyde (MDA) level,superoxide dismu-tase activity (SOD),the contents of protein and leucocytes in broncho-alveolar lavage fluid(BALF),and serum MDA level were determined in rats pretreated with allopurinol.In addition,the pathological changes of the lung tissues were also studied.It was found that early administration of allopurinol resulted in marked reduction of PMVP,and the protein content and leucocyte count in BALF.His-topathological examinations revealed that allopurinol could reduce the leucocyte accumulation in pulmonary vessels,interstitial leucocyte infiltration,interstitial and alveolar edema and hemorrhage,and vascular congestion.The serum and pulmonary levels of MDA also markedly decreased.The changes of pulmonary level of MDA were parallel to those of PMVP,and the protein content and leucocyte count in BALF in time course and in degree.The results listed here imply that the mechanism of the therapeutic effects of allopurinol on inhalation pulmonary injury is to reduce the production of superoxide anions through the inhibition of xanthine oxidase,in turn to inhibit the peroxidation of pulmonary lipids to alleviate pulmonary damage.