氨茶碱对平阳霉素致大鼠肺纤维化的干预作用

Intervention of amphylline on pingyangmycin induced pulmonary fibrosis in rats

目的:探讨氨茶碱对平阳霉素诱发的大鼠肺纤维化的干预作用及机制。方法:48只Wistar大鼠随机分为对照组、模型组和氨茶碱组,每组16只。后2组气管内滴入平阳霉素(5mg.kg-1)制备肺纤维化模型,滴入前1d分别经腹腔注入生理盐水和氨茶碱溶液(60mg.kg-1),对照组仅给予生理盐水;气管内滴药后第7d、28d分2批处理动物,收集血浆、支气管肺泡灌洗液(BALF)和肺组织标本。肺组织病理切片行HE和Masson染色,观察肺泡炎和肺纤维化程度;光镜下计数BALF中炎症细胞的数量;根据血浆与BALF上清中总蛋白的含量计算肺通透系数。采用放免法测定BALF中肿瘤坏死因子-α(TNF-α)水平和血浆中环腺嘌呤单核苷酸(cAMP)浓度,比色法测定肺匀浆中丙二醛(MDA)和羟脯氨酸(HYP)水平。结果:第7d,模型组肺泡炎明显,氨茶碱组病变较轻微;模型组BALF中炎症细胞总数、肺通透系数均高于对照组和氨茶碱组(P<0.01);模型组BALF中TNF-α活性和肺匀浆中MDA和HYP水平均高于对照组,氨茶碱组以上各指标均较模型组降低(P<0.05或0.01)。第28d,模型组出现肺纤维化和蜂窝肺,氨茶碱组病变明显减轻。模型组肺匀浆HYP水平明显高于氨茶碱组;但氨茶碱组血浆中cAMP浓度不论第7d、28d均高于模型组。结论:氨茶碱对平阳霉素诱发的肺纤维化有阻断作用,其机制可能与增加cAMP从而缓解肺泡炎有关。

Aim ： To investigate the effect and its mechanism of amphylline on pulmonary fibrosis induced by pingyangmyein. Methods：A total of 48 Wistar rats were randomly divided into three groups： the control group,the model group and the amphylline group. The latter 2 groups were intraperitoneally injected with normal saline （NS） and amphylline before making pulmonary fibrosis model by injecting pingyangmycin （5 mg · kg^-1 ） via trachea. The control group was injected with NS. At the 7th and 28th d after the establishment of model, the inflammatory cells in bronchoalveolar lavage fluid （BALF） were counted. The lung leakage coefficient （LLC） was calculated. The concentration of tumor necrosis factor （TNF-α） in BALF and cAMP in plasma was determined using radioimmunity assay. The contents of hydroxyproline（HYP） and MDA in lung tissue were also determined. Results： On the 7th d,the number of inflammatory cells and LLC in the model group were higher than those in the control group and amphylline group （P 〈0.01 ） ; on the 28th d, the HYP content, MDA and TNF-α in the model group was higher than those of the amphylline group and control group. The level of cAMP in plasma was higher than the model group whether on the 7 th or 28 th d. Conclusion： Amphylline can inhibit pulmonary fibrosis induced by pingyangmycin through elevating the level of cAMP,which alleviates alveolitis.