尿激酶对肺纤维化干预作用及对MMP-9和TIMP-1的影响被引量：1

Urokinase in the rat model of bleomycin-induced pulmonary fibrosis and its impact on the expression of matrix metalloproteinase9 and tissue inhibitor of metalloproteinase-1

在线阅读下载PDF

导出

摘要目的:探讨尿激酶型纤溶酶原激活剂(uPA)对肺纤维化的干预作用和对MMP-9/TIMP-1的影响。方法:SD雄性大鼠45只,随机分成3组:干预组(博莱霉素+尿激酶)、模型组(博莱霉素+生理盐水)和对照组。所有大鼠第28天处死。经HE、Masson胶原染色评价肺组织肺泡炎和肺纤维化程度。酶联免疫吸附法(ELISA)检测肺泡灌洗液中MMP-9、TIMP-1含量。结果:(1)肺泡炎程度评价:模型组为(1.7±0.6)分,干预组为(0.9±0.7)分,对照组为(0.2±0.4)分,模型组与干预组、对照组比较,差异有统计学意义(P<0.01)。(2)肺纤维化程度评价:模型组为(2.0±0.8)分,干预组为(1.1±0.7)分,组间差异有统计学意义(P<0.01)。(3)TIMP-1含量:模型组(1 240.8±90.3)pg/ml,对照组(1 078.3±31.6)pg/ml,干预组(1 163.6±69.6)pg/ml,模型组与对照组比较差异有统计学意义(P<0.01);模型组与干预组比较,差异有统计学意义(P<0.05)。结论:尿激酶能减轻博来霉素诱导的大鼠肺纤维化,可能是通过抑制TIMP-1途径起作用。 Objective： To study the effect of urokinase on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism. Methods： Forty five male SD rats were randomly divided into three groups： the model group, the control group and the urokinase treatment group, in which the rats were intratracheally instilled with bleomycin（Smg/kg）. From the second day after bleomycin challenge, by intraperitoneal injection every two days, the urokinase treatment group was given urokinase （27500U/kg）, the other two groups were given sterile saline. All the rats were sacrificed on Day 28. The lungs were harvested and evaluated by HE and Masson＇s trichrome stain. The level of MMP-9 and TIMP-1 in BALF were measured by ELISA. Results： On Day 28, alveolitis in the uPA group （0.9 ± 0.7 ） points, was significantly lower as compared with the model group （1.7 ±0.6）points, P 〈0.01; but higher than that of the control group（0. 2 ± 0.4 ）points, P 〈 0.05. Pulmonary fibrosis in the uPA group（ 1.1 ± 0.7 ）points vs the model group （2. 0 ±0.8） points, P 〈0.01. In the urokinase group,the concentration of TIMP-1 in BALF（ 1 163.6 ±69.6） pg/ml, reduced significantly as compared with that of the model group （ 1 240.8 ± 90.3 ） pg/ml , P 〈 0.05 ; but higher than that of the control group（ 1 078.3 ±31.6）pg/ml, P 〈0.05. Conclusion： Urokinase （uPA） alleviated bleomycin-induced pulmonary fibrosis in rats, inhibiting the expressions of TIMP-1 in lung tissues may be one of the mechanisms.

作者万兵郑金旭严玉兰黄新建吴建农

机构地区江苏大学附属医院呼吸科江苏大学附属医院病理科

出处《江苏大学学报（医学版）》 CAS 2007年第5期400-402,I0002,共4页 Journal of Jiangsu University：Medicine Edition

基金江苏省科技厅社会发展基金资助项目(BS2001020)

关键词尿激酶肺纤维化基质金属蛋白酶-9 基质金属蛋白酶抑制剂-1 urokinase pulmonary fibrosis matrix metalloproteinase-9 tissue inhibitor of metalloproteinase-1

分类号 R563 [医药卫生—呼吸系统] R332.2 [医药卫生—人体生理学]

作者简介万兵（1976-），男，硕士研究生；郑金旭（联系人），教授，搏导，E-mail：jxuzh135@163．com。

引文网络
相关文献

参考文献7

1Sisson TH,Hanson KE,Subbotina N,et al.Inducible lung-specific urokinase expression reduces fibrosis and mortality after lung injury in mice[J].Am J Physiol Lung Cell Mol Physiol,2002,283(5):1023-1032.
2Swaisgood CM,French EL,Noga C,et al.The development of bleomycin-induced pulmonary fibrosis in mice deficient for components of the fibrinolytic system[J].Am J Pathol,2000,157(1):177-187.
3Gong LK,Li XH,Wang H,et al.Feitai attenuates bleomycin-induced pulmonary fibrosis in rats[J].Biol Pharm Bull,2004,27(5):634-640.
4李圣青,张艰,黎志东,李焕章,戚好文.小鼠肺纤维化模型中基质金属蛋白酶-9及其抑制剂表达水平的变化[J].细胞与分子免疫学杂志,2004,20(6):723-726. 被引量：16
5Oggionni T,Morbini P,Inghilleri S,et al.Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis[J].Eur J Histochem,2006,50(4):317-325.
6Van Leer C,Stutz M,Haeberli A,et al.Urokinase plasminogen activator released by alveolar epithelial cells modulates alveolar epithelial repair in vitro[J].Thromb Haemost,2005,94(6):1257-1264.
7Jensen MK,Holten-Andersen MN,Riisbro R,et al.Elevated plasma levels of TIMP-1 correlate with plasma suPAR/uPA in patients with chronic myeloproliferative disorders[J].Eur J Haematol,2003,71(5):377-384.

二级参考文献6

1Sam L, Nicolas R, Brain GO, et al. Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers[J]. Am J Respir Crit Care Med, 2000, 162(4): 1355-1360.
2Jenny T.M, Donald PT, Paula NB, et al. All-trans retinoic acid modulates the balance of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in patients with emphysema[J]. Chest, 2003, 124: 1724-1732.
3Ruiz V, Ordonez RM, Berumen J, et al. Unbalanced collagenases/TIMP-1 expression and epithelial apoptosis in experimental lung fibrosis[J]. Am J Physiol Lung Cell Mol Physiol, 2003, 285(5): L1026-1036.
4Russell RE, Culpitt SV, DeMatos C, et al. Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease[J]. Am J Respir Cell Mol Biol, 2002,
5Lim S, Roche N, Oliver BG, et al. Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. Regulation by interleukin-10[J]. Am J Respir Crit Care Med, 2000, 162(4 Pt 1): 1355-1360.
6李圣青,李焕章,杨乔欣,倪殿涛.TGF-βRⅡ/Fc融合蛋白的纯化及其生物学活性鉴定[J].细胞与分子免疫学杂志,2003,19(4):400-402. 被引量：1