罗格列酮和强的松对博来霉素诱导大鼠肺纤维化中FIZZ1表达的影响

目的：观察Fizzl在肺组织中的动态表达及其意义，并比较罗格列酮与强的松对Fizzl表达的影响。方法：90只雄性SD大鼠随机分为对照组，模型组，强的松干预组，罗格列酮干预组，强的松＋罗格列酮干预组，模型组和干预组大鼠气管内一次性注入博来霉素构建大鼠肺纤维化模型，对照组给予等量生理盐水。造模24小时后各干预组给予相应药物灌胃。各组动物于7、14、28d随机处死6只，测肺系数，取肺组织病理切片行HE和Masson染色，观察肺泡炎和纤维化程度，测肺组织羟脯氨酸含量，免疫组化法检测Fizzl在肺组织中的表达情况。结果：干预组各时期肺纤维化程度均较模型组轻。Fizzl表达呈动态性变化，第7天表达最高，14d，28d表达减弱。干预组各时期Fizzl表达水平较模型组降低，其中罗格列酮和强的松联合干预组早期对Fizz的下调水平更大。结论：Fizzl的表达上调可能参与博来霉素诱导的肺纤维化形成；罗格列酮、强的松均可下调Fizzl表达减轻博来霉素诱导的肺纤维化程度，减少肺组织胶原的沉积，提示Fizzl可成为肺纤维化治疗的新靶点，罗格列酮和强的松联用治疗较单用强的松效果更好，对Fizzl的下调水平更大。

The Effects of Rosiglitazone and Prednisone on the Expression of FIZZ1 in the Pulmonary Fibrosis Induced by Blemycin

Objective： To estimate the effects of rosiglitazone, a PPAR-~ agonist, and prednisone on the dynamic expression of Fizzl in pulmonary fibrosis induced by bleomycin （BLM） in rats. Methods： Ninety adult male Sprague-Dawley （SD） rats were randomly divided into five groups： the normal group （group N）, bleomycin group （group B）, the prednisone group （group P）, rosiglitazone group （group R）, prednisone and rosiglitazone group （group P＋R）. Each group contained 18 rats. And the animals in each group at 7th, 14th, 28th days after modeling were randomly divided into 3 subgroups, each subgroup includes 6 rats. The BPF model was established by a single dosage of 5 mg/kg bleomycin intratraeheal, however group N was given the same dose of saline （NS） solution. After intratracheally instillation of BLM for 24h, the rats in each group received NS, prednisone, rosiglitazone or both prednisone and rosiglitazone by gavage per day. At 7th, 14th, 28th days after BLM administration, rats in per treatment group were randomly killed respectively. The lungs were harvested for lung index test, hemotoxylin and eosin stain, Masson＇s trichorome stain and determination of hydroxyproline content. The immtmohistochemical method was used to detect the expression of fizzl. Results： The degree of fibrosis in treatment group was lower than that in bleomycin group at every stage. Fizzl expression had a dynamic changes. The expression of fizzl protein in the lung increased after 7th days in bleomycin-trected animals, and slightly decreased at 14th days, and markedly decreased at 28th days. The expression of Fizzl in treatment group was lower than that in model group at all stage, the expression of fizzl in prednisone and rosiglitazone groups were downregulated more than those in other treatment groups. Conclusion： The upregulation of the expression of fizz I may participate in pulmonary fibrosis induced by bleomycin. Both prednisone and Rosiglitazone can downregulate the expression of fizzl, diminish the extent of pulmonary fibrosis induced by bleomycin, and decease the accumulation of extracellular matrix protein, suggesting that fizzl can become a new target in the treatment of pulmonary fibrosis.