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曲古抑菌素A对博莱霉素致肺纤维化小鼠NF-κB表达的影响研究
黄旭晴, 徐长青, 李旭
杭州师范大学附属医院呼吸科
摘要:
目的观察曲古抑菌素A(TSA)对博莱霉素(BLM)诱导的肺纤维化小鼠核因子-κB(NF-κB)表达的影响。方法96只健康雄性C57BL/6小鼠随机分为对照组、模型组、TSA早期干预组和TSA晚期干预组,各24只。模型组、TSA早期干预组和TSA晚期干预组小鼠均予以气管内滴注BLM(10mg/kg体重)溶液0.15ml诱导肺纤维化模型,对照组小鼠予0.9%氯化钠注射液0.15ml气管内滴注。建模后,TSA干预组分阶段(早期:第1~14天;晚期:第15~28天)予以TSA(40mg/kg体重)溶液腹腔注射,2次/周。模型组和对照组予以等体积二甲基亚砜腹腔注射作为溶媒对照。建模后第7、14、28天各组均随机分3批处死小鼠8只,留取右肺上叶组织行HE染色和Masson染色观察肺泡炎及肺纤维化程度,并行Szapiel评分,右肺中、下叶组织碱水解法检测羟脯氨酸(HYP)含量,免疫组化方法检测NF-κB表达水平。结果病理学检查比较,对照组小鼠肺泡结构正常,模型组小鼠肺组织在第7天出现出血、渗出等肺泡炎性改变,第28天出现明显肺纤维化。模型组小鼠肺组织各时点肺泡炎Szapiel评分、HYP含量、NF-κB表达水平均高于对照组(均P<0.05);TSA早期干预组小鼠各时点以上指标均低于模型组(均P<0.05),而TSA晚期干预组与模型组比较均无统计学差异(均P>0.05)。结论早期应用TSA或能通过抑制NF-κB的表达发挥延缓肺纤维化的作用。
关键词:  曲古抑菌素 A 肺间质纤维化 核因子 -κB
DOI:
分类号:
基金项目:杭州市社会发展自主申报项目;浙江省公益性技术应用研究计划项目;杭州市卫生科技计划项目
Trichostatin A affects expression of NF-κB in mice with bleomycin-induced pulmonary fibrosis
HUANG Xunqing, XU Changqing, LI Xu
the Affiliated Hospital of Hangzhou Normal University
Abstract:
Objective To investigate the effect of trichostatin A on expression of NF-κB in mice with bleomycin-induced pulmonary fibrosis. Methods Ninty-six male C57BL/6 mice were randomly allocated into four groups with 24 in each group: saline control group (control group), bleomycin-induced pulmonary fibrosis group (model group), early TSA treatment group (early group), and late TSA treatment group (late group). Eight mice in each group were sacrificed at d7, d14 and d28.The lung tissue samples were taken and hematoxylin eosin and Masson staining were adopted to evaluate the severity of pulmonary inflammation and fibrosis. The contents of hydroxypro1ine (HYP) in the lung tissues were detected by alkaline hydrolysis technique. Results The lung tissue in model group presented significant bleeding and effusion at d7 and pulmonary fibrosis at d28.Bleeding, effusion and pulmonary fibrosis were attenuated in early treatment group compared to model group at the same time points.Hydroxyproline content and the expression of NF-κB in lung tissue were significantly higher in model group than those in control group (both P<0.05). Compared with model group, early group showed milder alveolitis and lower Szapiel score of pulmonary fibrosis, decreased hydroxyprollne content and NF-κB expression at the same time points (both P<0.05). However, there were no significant differences in above indicators between late group and model group. Conclusion Early treatment of TSA can alleviate bleomycin-induced pulmonary fibrosis via inhibiting early inflammation and inhibiting expressions of NF-κB.
Key words:  TrichostatinA Pulmonary fibrosis NF-κB