摘要
目的观察沙利度胺对博来霉素所致大鼠肺纤维化的影响,并探讨其可能作用机制。方法选择健康雄性Wistar大鼠45只,随机分为正常对照组(N组)、肺纤维化模型组(M组)和沙利度胺治疗组(T组)3组,每组各15只。M组于气管内滴注博来霉素(BLM)5mg/kg生理盐水诱导肺纤维化,造模次日起每日腹腔内注射二甲基亚砜(DMSO)液;T组同样方法造模,次日起每日腹腔内注射沙利度胺(4mg/只)DMSO溶液;N组气管内滴注生理盐水,次日起每日腹腔内注射DMSO液。各组动物均于制模后的第7、14、28天分别随机处死5只动物,取肺组织行病理切片行苏木素-伊红(HE)染色和Masson染色,观察肺泡炎和肺纤维化程度;碱水解法检测肺组织羟脯氨酸(Hyp)含量;双抗夹心酶联免疫吸附试验(ELISA)法测定肺泡灌洗液(BALF)中转化生长因子β1(TGF-β1)及肿瘤坏死因子(TNF)-α的含量。结果 M组纤维化程度逐渐加重,于第28天形成明显的肺纤维化;其肺泡炎、纤维化评分,Hyp、TGF-β1、TNF-α的含量与N组比较均明显升高(P<0.05)。T组各时间点肺泡炎程度显著低于M组(P<0.05)。第14、28天,T组肺纤维化程度及肺组织Hyp含量较M组均明显降低(P<0.05)。此外,T组BALF中TGF-β1、TNF-α的含量亦低于M组,差异有统计学意义(P<0.05)。结论沙利度胺可减轻BLM诱导的大鼠肺纤维化,其作用机制可能是通过下调TGF-β1及TNF-α在肺内的表达而实现的。
Objective To investigate the effects of Thalidomide on bleomycin-induced pulmonary fibrosis in rats and to study the possible mechanism. Methods Forty-five healthy male wistar rats were randomized into three groups： normal control group （group N） , pulmonary fibrosis model group （group M） and thalidomide group （group T）, with 15 rats in each group. The group M received intra-tracheal instillation of 5 mg/kg bleomycin （BLM） for modeling of pulmonary fibrosis, and intraperitoneal injection with daily DMSO on the next day; group T received BLM in the same, and intraperitoneal injection with 4 mg Thalidomide （dissolved in DMSO）; group N was injected intraperitoneally with DMSO after intratracheal instillation of saline. Every five rats in each group were sacrificed at random for pathological sections of lung on days 7, 14 and 28 after modeling, respectively. The degree of pulmonary alveolitis and pulmonary fibrosis was evaluated by staining with HE and trichrome masson staining. The level of hydroxyproline （Hyp） in the lung tissue was examined by alkaline hydrolysis, and the levels of TGF-β1 and TNF-α in BLAF measured with double antibody sandwich ELISA. Results In group M, pulmonary fibrosis increased gradually and became significant on day 28, with higher scores of alveolitis and fibrosis, and higher levels of Hyp, TGF-β1 and TNF-α compared with those in group N（P〈0.05）. Group T showed significantly less fibrosis than group M at all time points （P〈0.05）, and compared with group M, the score of pulmonary fibrosis and level of Hyp were apparently lowered on days 14 and 28 （P〈0.05）. Moreover, the levels of TGF-β1 and TNF-α in BALF in group T were also significantly lower than those in group M （P〈0.05）. Conclusion Thalidomide may alleviate the degree of bleomycin-induced pulmonary fibrosis in rats by down-regulating the expressions of TGF-β1 and TNF-α in the lungs.
出处
《中国药物与临床》
CAS
2010年第12期1346-1349,共4页
Chinese Remedies & Clinics
基金
山西省科技攻关计划项目(20080311059-5)
关键词
转化生长因子Β1
肿瘤坏死因子Α
肺纤维化
沙利度胺
Transforming growth factor beta1
Tumor necrosis factor-alpha
Pulmonary fibrosis
Thalidomide
