引用本文
  • 宋立成,韩志海*,李虎明,孟激光,陈旭昕,吴晶.糖皮质激素减轻烟雾吸入性大鼠急性肺损伤后肺纤维化[J].第二军医大学学报,2019,40(1):31-37    [点击复制]
  • SONG Li-cheng,HAN Zhi-hai*,LI Hu-ming,MENG Ji-guang,CHEN Xu-xin,WU Jing.Glucocorticoid attenuating pulmonary fbrosis in rats with acute lung injury induced by smoke inhalation[J].Acad J Sec Mil Med Univ,2019,40(1):31-37   [点击复制]
【打印本页】 【下载PDF全文】 【HTML】 查看/发表评论下载PDF阅读器关闭

←前一篇|后一篇→

过刊浏览    高级检索

本文已被:浏览 295次   下载 200 本文二维码信息
码上扫一扫!
糖皮质激素减轻烟雾吸入性大鼠急性肺损伤后肺纤维化
宋立成,韩志海*,李虎明,孟激光,陈旭昕,吴晶
0
(解放军总医院第六医学中心呼吸与危重症医学科, 北京 100048
*通信作者)
摘要:
目的 探究早期应用不同时程甲泼尼龙(MP)对大鼠烟雾吸入性肺损伤后期纤维化的改善作用。方法 178只成年雄性SD大鼠随机分为对照组(n=18)、单纯烟雾吸入组(smoke组,n=40)、烟雾吸入+MP1 d治疗组[smoke+MP(1D)组,n=40]、烟雾吸入+MP 3 d治疗组[smoke+MP(3D)组,n=40]、烟雾吸入+MP 7 d治疗组[smoke+MP(7D)组,n=40]。烟雾吸入大鼠在烟雾箱中烟雾暴露30 min以达到急性肺损伤标准,之后分别于烟雾吸入的1 d、1~3 d、1~7 d给予腹腔注射MP(每天4 mg/kg),计算大鼠28 d生存率;烟雾吸入后的第7、14、28天取大鼠肺组织行马松三色染色、天狼星红染色,并进行肺纤维化评分;通过实时荧光定量PCR测定大鼠肺组织中转化生长因子β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)的mRNA表达;通过蛋白质印迹法测定大鼠肺组织中髓过氧化物酶(MPO)、结缔组织生长因子(CTGF)、高迁移率族蛋白1(HMGB1)、白细胞介素6(IL-6)的表达情况。结果 Smoke组大鼠烟雾吸入28 d生存率为47.50%,给予不同时程MP治疗后,生存率均提高至80%以上(P均<0.01)。马松三色染色及天狼星红染色结果显示smoke组大鼠肺纤维化程度加重,而smoke+MP(3D)组和smoke+MP(7D)组较smoke组和smoke+MP(1D)组纤维化程度改善,胶原沉积减轻(P<0.05或P<0.01)。烟雾吸入后smoke组和smoke+MP(1D)组大鼠肺组织中TGF-β1α-SMA的mRNA表达水平逐步升高,28 d时smoke组和smoke+MP(1D)组高于smoke+MP(3D)和smoke+MP(7D)组(P<0.05或P<0.01)。烟雾吸入后28 d时smoke+MP(3D)组和smoke+MP(7D)组大鼠肺组织中MPO、CTGF、HMGB1、IL-6的表达水平低于smoke组和smoke+MP(1D)组(P<0.05,P<0.01)。但smoke+MP(3D)组和smoke+MP(7D)组上述指标差异均无统计学意义(P均>0.05)。结论 大鼠烟雾吸入后给予MP治疗可以提高其生存率,3 d或7 d的MP治疗可以改善大鼠28 d肺纤维化程度,但这两种治疗方案之间差异无统计学意义。
关键词:    肺损伤  甲泼尼龙  肺纤维化
DOI:10.16781/j.0258-879x.2019.01.0031
投稿时间:2018-07-20修订日期:2018-10-29
基金项目:军队后勤科研计划重点项目(BHJ16J011),解放军总医院第六医学中心创新培育基金(CXPY 201729).
Glucocorticoid attenuating pulmonary fbrosis in rats with acute lung injury induced by smoke inhalation
SONG Li-cheng,HAN Zhi-hai*,LI Hu-ming,MENG Ji-guang,CHEN Xu-xin,WU Jing
(Department of Respiratory and Critical Care Medicine, Sixth Medical Center, General Hospital of PLA, Beijing 100048, China
*Corresponding author)
Abstract:
Objective To explore the effect of methylprednisolone (MP) with different durations on pulmonary fibrosis in rats with acute lung injury induced by smoke inhalation.Methods A total of 178 male SD rats were randomized into 5 groups:control group (n=18), simple smoke inhalation group (smoke group, n=40), smoke inhalation+ MP treatment for 1 d, 3 d and 7 d groups, naming smoke+MP (1D) group (n=40), smoke+MP (3D) group (n=40) and smoke+MP (7D) group (n=40), respectively. The rats were exposed to smoke for 30 min in the smoke box to meet the criteria of acute lung injury. MP (4 mg/kg per day) was injected intraperitoneally at 1 d, 1-3 d and 1-7 d after smoke inhalation. Survival rates were calculated at 28 d after smoke inhalation. At 7 d, 14 d and 28 d after smoke inhalation, the lung tissues were stained with Masson's trichrome staining and Sirius Red staining to evaluate pulmonary fibrosis. The mRNA expression levels of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by real-time fluorescent quantitative PCR, and the expression levels of myeloperoxidase (MPO), connective tissue growth factor (CTGF), high mobility group box 1 (HMGB1) and interleukin 6 (IL-6) were detected by Western blotting.Results The survival rate of the rats in the smoke group was 47.50%, and the survival rates were significantly improved to more than 80% after MP treatment with different durations (all P<0.01). Masson's trichrome staining and Sirius Red staining staining showed that the lung fibrosis of the rats in the smoke group was aggravated, and the fibrosis and collagen deposition in the smoke+MP (3D) and smoke+ MP (7D) groups were significantly attenuated compared with the smoke and smoke+MP (1D) groups (P<0.05 or P<0.01). As time progressed, the mRNA expression levels of TGF-β1 and α-SMA after smoke inhalation were increased in the smoke and smoke+MP (1D) groups. At 28 d after smoke inhalation, the TGF-β1 and α-SMA mRNA levels were significantly higher in the smoke and smoke+MP (1D) groups compared with the smoke+MP (3D) and smoke+MP (7D) groups (P<0.05 or P<0.01). At 28 d after smoke inhalation, the protein expression levels of MPO, CTGF, HMGB1 and IL-6 were significantly reduced in smoke+MP (3D) and smoke+MP (7D) groups compared with the smoke and smoke+MP (1D) groups (P<0.05, P<0.01). However, the above indicators have no significant difference between smoke+MP (3D) group and smoke+MP (7D) group (all P >0.05).Conclusion MP can significantly improve survival rate of rats with smoke inhalation injury. MP treatment for 3 d or 7 d can significantly attenuate smoke inhalation induced pulmonary fibrosis at 28 d after smoke inhalation, but there is no significant difference between these two treatment protocols.
Key words:  smoke  lung injury  methylprednisolone  pulmonary fibrosis