Effect of Different Administration Methods with Bleomycin on Pulmonary Fibrosis in Rats

He WANG; Guang-ping ZHANG; Hong-ping HOU; Yun-hang GAO; Shuang-rong GAO; Meng MA; Hai-jing ZHANG; Zhong-xiu ZHANG; Teng-fei CHEN; Ping SU; Ling SONG; Yi-fei YANG; Jiang LI; Zu-guang YE

doi:10.13422/j.cnki.syfjx.20191104

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Effect of Different Administration Methods with Bleomycin on Pulmonary Fibrosis in Rats

Pharmacology | 更新时间：2021-02-09

- Effect of Different Administration Methods with Bleomycin on Pulmonary Fibrosis in Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 11, Pages: 73-79(2019)
- 作者机构：
  
  1.贵阳中医学院，贵阳　 550002；
  2.中国中医科学院　中药研究所，北京　 100700
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191104
  CLC： R2-0; R22; R285.5
- Received：19 October 2018，
  
  Published Online：20 February 2019，
  
  Published：05 June 2019
- 稿件说明：
移动端阅览
He WANG, Guang-ping ZHANG, Hong-ping HOU, et al. Effect of Different Administration Methods with Bleomycin on Pulmonary Fibrosis in Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(11): 73-79.
DOI：

He WANG, Guang-ping ZHANG, Hong-ping HOU, et al. Effect of Different Administration Methods with Bleomycin on Pulmonary Fibrosis in Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(11): 73-79. DOI： 10.13422/j.cnki.syfjx.20191104.

摘要

目的：

比较博来霉素(BLM)气管灌注、尾静脉注射及雾化吸入致大鼠肺纤维化模型的优劣，以便筛选出最佳的给药途径。

方法：

选择SPF级雄性SD大鼠80只，采用体重随机分组法将其分为正常组，单次气管灌注组(10 mg·kg

－1

)，多次气管灌注组(5 mg·kg

－1

)，单次静脉注射组(150 mg·kg

－1

)，多次静脉注射组(50 mg·kg

－1

)，单次雾化吸入模型组(30 min)，多次雾化吸入模型组(30 min)。观察给药后7，14，28 d各组大鼠死亡情况及体质量变化。给药后28 d，观察各组大鼠肺系数，取大鼠肺组织制备石蜡切片并进行苏木素-伊红(HE)及马松(Masson)染色，并通过酶联免疫吸附测定(ELISA)检测肺组织中羟脯氨酸(HYP)和纤溶酶原激活物抑制剂-1(PAI-1)含量，评价各组大鼠肺泡炎及肺纤维化程度。

结果：

与正常组比较，气管灌注组的大鼠死亡率在所有药物处理组中最高。大鼠肺系数的测定结果显示，与正常组比较，多次静脉注射组和多次雾化吸入组大鼠的肺系数显著升高(

0.05，

0.01)。雾化造模组较高于其他模型组，多次雾化模型组高于单次雾化模型组。大鼠HE及Masson染色结果提示，气管灌注组、静脉注射组和多次雾化吸入组大鼠肺组织中肺间隔增厚和肺间质纤维化程度较高，其中多次雾化模型组较其他组肺纤维化程度最为明显。ELISA结果发现，与正常组比较，雾化吸入组和气管灌注组大鼠肺组织中HYP和PAI-1含量显著升高(

0.05)。多次雾化吸入组与单次雾化吸入组显著高于其他造模组。

结论：

多次雾化吸入博来霉素制备肺纤维化模型，造模大鼠的病理损伤和生理指标相对稳定，符合肺纤维化的演变过程，是一种有效的肺纤维化模型制备手段。

Abstract

Objective:

Compare the effects of 3 administration methods (tracheal perfusion

tail vein injection and aerosol inhalation) with bleomycin (BLM) in inducing pulmonary fibrosis in rats

in order to find out the optimal administration methods.

Method:

Eighty sprague-dawley (SD) male rats with SPF were randomly divided into aerosol inhalation blank group

single tracheal perfusion group(10 mg·kg

-1

)

multiple tracheal perfusion group(5 mg·kg

-1

)

single intravenous injection group(150 mg·kg

-1

)

multiple intravenous injection group(50 mg·kg

-1

)

single aerosol inhalation group (30 min)and multiple aerosol inhalation group(30 min). The mortality and body weight of rats in each group were observed at 7 d

14 d and 28 d after the administration. And 28 days later after the administration

the lung coefficients of rats in each group were observed

paraffin sections were prepared

hematoxylin-eosin staining (HE) and Masson staining were performed

and the contents of hydroxyproline (HYP) and plasminogen activator inhibitor-1 (PAI-1) in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA)

so as to evaluate the alveoli inflammation and pulmonary fibrosis of rats in each group.

Result:

Compared with the aerosol inhalation blank group

the rats in the trachea perfusion group had the highest mortality among the drug treatment groups. The pulmonary coefficients of rats in the multiple intravenous injection group and the multiple inhalation group were significantly higher than those in the blank group(

0.05

0.01). The multiple inhalation group was higher than the other model group and the single atomization model group. The results of HE and Masson staining showed thickening of pulmonary septum and higher degree of pulmonary interstitial fibrosis in tracheal perfusion group

intravenous injection group and multiple inhalation group. The degree of pulmonary fibrosis in the multiple inhalation group was more obvious than that in other groups. The results of ELISA showed that the levels of HYP and PAI-1 in lung tissues of rats in aerosol inhalation group and tracheal perfusion group were significantly higher than those in control group(

0.05). The multiple inhalation group and the single atomization inhalation group were significantly higher than other modules.

Conclusion:

Bleomycin was inhaled repeatedly to establish pulmonary fibrosis model. The pathological injury and physiological indexes of the model rats were relatively stable

which conforms with the evolution process of pulmonary fibrosis.

关键词

Keywords

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