雾化蚯蚓纤溶酶对博莱霉素诱导的大鼠肺纤维化的影响

[Effects of aerosolized earthworm fibrinolytic enzyme on bleomycin induced pulmonary fibrosis in rats].

作者信息

Xue Yi, Dai Hua-ping, Cui Ai, Niu Shu-jie, Pang Bao-sen

机构信息

Department of Respiratory & Critical Care Medicine, Capital Medical University, Beijing, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2012 Dec 25;92(48):3429-33.

PMID:23327706

Abstract

OBJECTIVE

To explore the effects of aerosolized earthworm fibrinolytic enzyme (EFE) on bleomycin-induced pulmonary fibrosis in rats.

METHODS

A total of 72 male SD rats were divided randomly into 3 groups of bleomycin (BLM) group with intratracheal BLM (5 mg/kg), control group with the same dose of normal saline, then after both receiving aerosolization of normal saline once daily instead of EFE, EFE group with EFE (2500 U/kg) by aerosolization once daily after BLM instillation. Lung histopathology, immunohistochemistry for transforming growth factor β(1) (TGF-β(1)), lung hydroxyproline contents, levels of urokinase PA (uPA), tissue plasminogen activator (tPA) and PA inhibitor 1 (PAI-1) in lung and blood were observed at Days 7, 14 and 28 of experiment, respectively.

RESULTS

Compared with BLM group, pulmonary fibrosis improved and the TGF-β(1) expression of lung tissue decreased (P < 0.01). Hydroxyproline content of lung tissue decreased in EFE group compared with BLM group ((5.8 ± 2.5) vs (9.6 ± 1.3), (6.7 ± 1.4) vs (9.7 ± 1.5), (7.5 ± 1.2) vs (9.7 ± 1.4) mg/L, P < 0.01). Compared with BLM group, the uPA levels of lung were elevated in EFE group at Days 7 and 14 ((1.04 ± 0.36) vs (0.72 ± 0.11), (0.90 ± 0.09) vs (0.75 ± 0.08) µg/L, P < 0.05). Moreover, the plasma levels uPA of increased at Days 14 and 28 ((0.32 ± 0.04) vs (0.25 ± 0.02), (0.36 ± 0.05) vs (0.28 ± 0.04) µg/L, P < 0.05). Consistently, compared with BLM group, the tPA levels of lung increased in EFE group ((4.70 ± 0.87) vs (3.01 ± 0.62), (5.72 ± 0.37) vs (3.00 ± 0.51), (6.73 ± 1.12) vs (3.18 ± 0.38) µg/L, P < 0.01) and the plasma levels of tPA also increased ((3.40 ± 0.36) vs (1.79 ± 0.38), (3.17 ± 0.37) vs (2.18 ± 0.17), (3.85 ± 0.56) vs (2.80 ± 1.06) µg/L, P < 0.01). However, compared with BLM group, the PAI-1 levels of lung decreased in EFE group ((6.04 ± 0.81) vs (8.52 ± 1.01), (6.78 ± 0.81) vs (9.81 ± 1.73), (7.63 + 0.99) vs (11.44 ± 2.54), P < 0.05) and the plasma levels of PAI-1 also decreased in EFE group ((4.82 ± 0.42) vs (6.89 ± 0.84), (5.73 ± 0.40) vs (7.30 ± 1.09), (5.64 ± 0.87) vs (7.98 ± 1.10) µg/L, P < 0.05).

CONCLUSIONS

Earthworm fibrinolytic enzyme may decrease bleomycin-induced pulmonary fibrosis and TGF-β(1) expression while increasing fibrinolytic activation. And fibrinolytic strategies are probably useful for the therapy of fibrotic lung diseases.

摘要

目的

探讨雾化蚯蚓纤溶酶（EFE）对博莱霉素诱导的大鼠肺纤维化的影响。

方法

将72只雄性SD大鼠随机分为3组，博莱霉素（BLM）组经气管内注入BLM（5mg/kg），对照组注入相同剂量的生理盐水，两组均每日雾化生理盐水而非EFE；EFE组在注入BLM后每日雾化EFE（2500U/kg）。分别在实验第7、14和28天观察肺组织病理学、转化生长因子β(1)（TGF-β(1)）免疫组化、肺羟脯氨酸含量、肺和血液中尿激酶型纤溶酶原激活剂（uPA）、组织型纤溶酶原激活剂（tPA）及纤溶酶原激活剂抑制物1（PAI-1）水平。

结果

与BLM组相比，EFE组肺纤维化改善，肺组织TGF-β(1)表达降低（P<0.01）。EFE组肺组织羟脯氨酸含量低于BLM组（(5.8±2.5)对(9.6±1.3)、(6.7±1.4)对(9.7±1.5)、(7.5±1.2)对(9.7±1.4)mg/L，P<0.01）。与BLM组相比，EFE组在第7和14天肺组织uPA水平升高（(1.04±0.36)对(0.72±0.11)、(0.90±0.09)对(0.75±0.08)μg/L，P<0.05），且在第14和28天血浆uPA水平升高（(0.32±0.04)对(0.25±0.02)、(0.36±0.05)对(0.28±0.04)μg/L，P<0.05）。同样，与BLM组相比，EFE组肺组织tPA水平升高（(4.70±0.87)对(3.01±0.62)、(5.72±0.37)对(3.00±0.51)、(6.73±1.12)对(3.18±0.38)μg/L，P<0.01），血浆tPA水平也升高（(3.40±0.36)对(1.79±0.38)、(3.17±0.37)对(2.18±0.17) (3.85±0.56)对(2.80±1.06)μg/L，P<0.01）。然而，与BLM组相比，EFE组肺组织PAI-1水平降低（(6.04±0.81)对(8.52±1.01)、(6.78±0.81)对(9.81±1.73)、(7.63 + 0.99)对(11.44±2.54)，P<0.05），血浆PAI-1水平也降低（(4.82±0.42)对(6.89±0.84)、(5.73±0.40)对(7.30±1.09)、(5.64±0.87)对(7.98±1.10)μg/L，P<0.05）。