摘要
目的观察血必净联合甲泼尼龙对博莱霉素诱导的肺纤维化大鼠模型的干预作用。方法将Wistar大鼠80只按随机数字表法随机分成5组：空白组、模型对照组、血必净组、甲泼尼龙组及联合干预组。除空白组外，其余4组以气管内滴注博莱霉素（5mg／kg）建立模型。建模后第2天始空白组和模型对照组腹腔注射生理盐水9ml·kg-1·d-1，血必净组腹腔注射血必净4．5m1·kg-1·d-1及生理盐水4．5ml·kg-1·d-1，甲泼尼龙组腹腔注射1g／L的甲泼尼龙4．5ml·kg-1·d-1及生理盐水4．5ml·kg-1·d-1，联合干预组腹腔注射1g／L的甲泼尼龙4．5ml·kg-1·d-1及血必净4．5ml·kg-1·d-1。于造模后第14、28天取材。采用HE及MASSON染色法观察肺组织病理变化，酶联免疫吸附（ELISA）法检测血清白细胞介素6（IL-6）、肿瘤坏死因子d（TNF-α）的水平，免疫组织化学染色检测肺组织内转化生长因子β1（TGF-β1）的表达水平。结果联合干预组第14和28天肺泡炎评分[（1．09±0．30）比（2．03±0．25）分和（0．75±0．27）比（1．78±0．36）分]、肺间质纤维评分[（0．91±0．19）比（1．34±0．23）分和（0．75±O．27）比（1．78±0．36）分]、肺组织TGF-β1表达水平[（12．11±3．06）％比（17．70±2．70）％和（10．96±2．53）％比（16．72±2．20）％]、血清TNF-α水平[（68．39±9．28）比（90．94±11．16）ng／L和（67．14±10．88）比（81．73±7．23）ng／L]均显著低于模型对照组（均P〈0．05）；第14天血清IL-6水平也显著低于模型对照组[（1994-31）比（250±43）ng／L，P=0．036]，但第28天时差异无统计学意义[（192±25）比（227±24）ng／L，P=0．058]。结论血必净联合甲泼尼龙更能显著减轻大鼠肺组织肺泡炎及肺纤维化程度，其机制与降低血清IL-6、TNF-α水平以及肺组织TGF-β1表达水平相关。
Objective To explore the effect of Xuebijing plus methylprednisolone in a rat model of pulmonary fibrosis induced by bleomycin. Methods Eighty Wister rats were randomly divided into 5 groups of control, model control, Xuebijing, methylprednisolone and combined treatment （Xuebijing plus methylprednisolone）. Pulmonary fibrosis model was induced by an intra-tracheal injection of bleomycin. The treatment groups were administrated with 4. 5 ml · kg-1· d-1 Xuebijing and 4. 5 ml· kg-1 · d-1 physiologic saline, 4. 5 ml ·kg- 1 · d- 1 methylprednisolone and 4. 5 ml ·kg-1 · d- 1 physiologic saline, or 4. 5 ml · kg- 1 · d- 1 methylprednisolone and 4. 5 ml · kg- 1 · d- 1 Xuebijing respectively by intraperitoneal injection. And the control and model control groups received 9 ml · kg-1· d- 1 physiological saline. The animals were sacrificed at Days 14 and 28 respectively. The degrees of lung inflammation and pulmonary fibrosis were detected by hematoxylin ＆ eosin and Masson staining. The serum levels of interleukin-6 （ IL-6 ） and tumor necrosis factor-alpha （TNF-α） were assessed by enzyme-linked immunosorbent assay （ELISA）. The expression of transforming growth faetor-β1 （ TGF-β1 ） in lung tissue was evaluated by immunohistochemieal staining. Results Compared between the combined treatment and model control groups, at Days 14 and 28, the degree of alveolitis （ （ 1.09 ±0. 30） vs （2. 03 ±0. 25） and （0. 75 ±0. 27） vs （ 1.78 ±0. 36） ng/L）, the degree of pulmonary fibrosis（（0.91±0. 19 ）vs （1.34 ±0.23） and （0.75 ±0.27） vs （1.78 ± 0. 36） ）. The expression of TGF-β1 in lung tissue （ （ 12. 11 ±3.06） % vs （ 17.70± 2. 70） % ＆ （ 10. 96 ±2. 53）% vs （ 16. 72±2. 20）% ）. And the serum level of TNF-α（ （68.39± 9. 28） vs （90. 94 ± 11.16） ng/L ＆ （67.14 ± 10. 88 ） vs （81.73 ± 7.23 ） ng/L） all significantly decreased （ all P 〈 0. 05 ）. At Day 14,the serum level of IL-6 in the combined treatment group significantly decreased as compared with the model control group （ （ 199 ±31 ） vs （250± 43 ） ng/L, P = 0. 036）. At Day 28, no statistic difference was found （ （ 192 ± 25 ） vs （227 ± 24） ng/L, P = 0. 058 ）. Conclusions The combined treatment of methylprednisolone and Xuebijing is more effective in a rat model of pulmonary fibrosis. And its mechanism is associated with the reduced levels of IL-6 and TNF-α and TGF-β1 expression in lung tissue.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2014年第4期301-305,共5页
National Medical Journal of China
关键词
肺纤维化
甲泼尼龙
博莱霉素
血必净
大鼠
Pulmonary fibrosis
Methylprednisolone
Bleomycin
Xuebijing
Rats
