Bryan C L, Lewis R E, Owens S L, Emanuel B, Jenkinson S G
Department of Medicine, University of Texas Health Science Center, San Antonio.
J Appl Physiol (1985). 1993 Jul;75(1):357-63. doi: 10.1152/jappl.1993.75.1.357.
Allopurinol is a potent xanthine oxidase inhibitor that has been administered to animals to protect tissues from oxidant injury. We hypothesized that allopurinol may protect against oxidant injury by inhibiting the inflammatory response. Male Sprague-Dawley rats were injected daily with vehicle or allopurinol and compared with noninjected controls. Animals were exposed to room air or 90% oxygen for 14 days. At the end of the exposure period, all animals were lavaged and bronchoalveolar lavage fluid (BALF) was examined for cell counts, lactate dehydrogenase (LDH), and protein. BALF neutrophils were significantly increased in oxygen-exposed noninjected controls (33 +/- 7 x 10(3)/mm3) and also in the vehicle-inoculated oxygen-exposed animals (43 +/- 6 x 10(3)/mm3). Allopurinol treatment resulted in a decrease in the neutrophilic alveolar response in oxygen-exposed animals (5.3 +/- 4 x 10(3)/mm3, P < 0.001). These data reveal that oxygen exposure produces a neutrophilic alveolar response that is attenuated by allopurinol treatment. BALF protein and LDH were significantly increased in all inoculated and noninoculated oxygen-exposed animals compared with air-exposed animals. Therefore, allopurinol decreases the neutrophilic alveolar response produced by a hyperoxic exposure in the rat but does not decrease lung injury as assessed by alveolar LDH and protein release.
别嘌醇是一种强效的黄嘌呤氧化酶抑制剂，已用于动物实验以保护组织免受氧化损伤。我们推测别嘌醇可能通过抑制炎症反应来预防氧化损伤。雄性Sprague-Dawley大鼠每日注射赋形剂或别嘌醇，并与未注射的对照组进行比较。动物暴露于室内空气或90%氧气环境中14天。在暴露期结束时，对所有动物进行灌洗，并检测支气管肺泡灌洗液（BALF）中的细胞计数、乳酸脱氢酶（LDH）和蛋白质。在暴露于氧气的未注射对照组（33±7×10³/mm³）以及接种赋形剂且暴露于氧气的动物（43±6×10³/mm³）中，BALF中性粒细胞显著增加。别嘌醇治疗使暴露于氧气的动物的中性粒细胞肺泡反应减少（5.3±4×10³/mm³，P<0.001）。这些数据表明，氧气暴露会产生中性粒细胞肺泡反应，而别嘌醇治疗可使其减弱。与暴露于空气的动物相比，所有接种和未接种且暴露于氧气的动物的BALF蛋白质和LDH均显著增加。因此，别嘌醇可减少大鼠高氧暴露产生的中性粒细胞肺泡反应，但根据肺泡LDH和蛋白质释放评估，其并未减轻肺损伤。
