不同剂量地塞米松对博莱霉素致大鼠肺纤维化的影响  

Influence of different dosages of dexamethasone on bleomycin-induced lung fibrosis in rats

作　　者：王克俭[1] 李惠萍[1] 陈宝[1] 

机构地区：[1]同济大学附属上海市肺科医院呼吸科,上海200433

出　　处：《临床肺科杂志》2009年第9期1195-1197,共3页Journal of Clinical Pulmonary Medicine

基　　金：国家自然科学基金资助项目(No30671996);上海市优秀学科带头人计划(No08XD14034);上海市科委科研基金资助项目(No064107050;044107050;044119637;08411961000;0852nm05600)

摘　　要：目的观察不同剂量地塞米松(DXM)对博莱霉素致大鼠肺纤维化的治疗作用及其副作用,探索DXM治疗动物肺纤维化的有效安全剂量。方法144只健康雄性SD大鼠随机分为4组:对照组(n=18)、DXM副作用观察组(n=54)、模型组(n=18)、DXM疗效观察组(n=54)。根据DXM剂量不同将DXM副作用观察组和DXM疗效观察组分为1mg/kg、2mg/kg、3mg/kg三个亚组,每亚组18只,再根据观察时间的不同将每亚组分为观察14d、28d、56d三个小组,每小组6只。根据观察时间的不同将对照组和模型组分为观察14d、28d、56d三个小组,每小组6只。观察到期后,统计大鼠存活情况;大鼠左肺病理切片HE染色,光镜下观察肺部炎症和纤维化程度;对照组、模型组和DXM疗效观察组大鼠右肺测定羟脯氨酸(HYP)含量;大鼠肝、肾组织切片HE染色,光镜下观察其组织结构、炎症反应等变化。采用SPSS13.0软件,P<0.05为差异有统计学意义。结果DXM副作用观察3mg/kg组的56d死亡率与相应对照组及DXM副作用观察1mg/kg组比较差异有统计学意义(P<0.05);DXM疗效观察3mg/kg组的56d死亡率与相应对照组、模型组、DXM疗效观察1mg/kg组比较差异有统计学意义(P<0.05)。DXM在一定程度上能减轻博莱霉素致肺纤维化大鼠的肺泡炎和纤维化程度,但随其剂量的增加和用药时间的延长,其致肺部感染的机率也增加。绝大多数DXM疗效观察组HYP含量均较相应模型组为低,差异有统计学意义(P<0.05),三个剂量的DXM疗效观察组间差异无统计学意义(P>0.05)。DXM副作用观察组和DXM疗效观察组大鼠肝组织普遍存在脂肪变性,而其肾组织可见肾小管内炎性细胞浸润。结论1mg/kg的DXM既能改善肺纤维化又未致严重感染和大鼠死亡率的增加,是治疗大鼠肺纤维化的有效安全剂量。Objective To observe the therapeutic and side effect of different dosages of dexamethasone（DXM） on bleomycin-induced lung fibrosis in rats and to investigate the effective and safe dosage of DXM on lung fibrosis models. Methods 144 healthy male Sprague-Dawley （SD） rats were randomly divided into four groups including control group （n = 18 ）, DXM side effect group （n = 54 ）, model group （n = 18 ） and DXM treated group （n = 54）. DXM side effect group and DXM treated group were then divided into three subgroups respectively （18 rats in each subgroup） according to different dosages of DXM including 1 mg/kg, 2 mg/kg and 3 mg/kg subgroup. Finally,each group was divided into three groups randomly （6 rats each group） ,which were sacrificed on 14 d, 28 d and 56 d. Survival analysis was done and HE staining was performed on the left lung tissue sections to observe the extent of alveolitis and fibrosis. Hydroxyproline （HYP） assays of the right lung tissue of rats in the control group, the model group and DXM treated group were also made to estimate the collagen content. The liver and kidney tissue sections were got HE stained to observe the structure and inflammation. Results The death rate by 56 d of 3 mg/kg DXM side effect group and the treated group was significantly higher as compared to that of homologous the control group, model group, 1 mg/kg DXM side effect group and the treated group （P 〈 0. 05 ）. The alveolitis and fibrosis induced by bleomyein could be relieved by DXM in some extent, while the infection rate was higher with the increase of its dosage and treated durations, and no more improvement was shown on lung fibrosis. HYP analysis showed that most of the treated groups had a lower content of collagen than the homologous model groups and there was no significant difference of HYP among the treated groups which were treated by three different dosages of DXM respectively. The livers in the DXM side effect groups and the treated groups got fatty degeneration generally,

关 键 词：地塞米松 肺纤维化 博莱霉素 副作用 

分 类 号：R563.9[医药卫生—呼吸系统]