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Journal of Chinese Integrative Medicine ›› 2004, Vol. 2 ›› Issue (6): 435-439.doi: 10.3736/jcim20040610

• Original Experimental Research • Previous Articles     Next Articles

Function of MMP/TIMP on airway remodeling of bronchial asthma and treating effects of Zhichuan Capsule

Yin-gen Wu1, Li-xin Wang2   

  1. 1. Respiratory Department, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
    2. Respiratory Department, Shanghai Hospital of Traditional Chinese Medicine, Shanghai 200071, China
  • Received:2004-03-16 Online:2004-11-20 Published:2018-10-20

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Objective: To explore the mechanism of the bronchial asthma and to study the treating effects of Zhichuan Capsule on the airway remodeling of asthmatic model rats.Methods: The rat model was established by being sensitized and activated with different density of ovalbumin through prolonged and repeated exposure for 8 weeks. The rats were randomly divided into model group, Zhichuan Capsule treated group, dexameson treated group, and Zhichuan Capsule and dexameson treated group. Another group of normal rats were taken as control. General histological changes were observed by hematoxylin and eosin stained sections. Being standardized by internal perimeter (Pi), the wall thickness (d), internal area (Ai), outer area (Ao) and wall area (WA) of the airway were quantified by computer-assisted image analysis system. The express of MMP-9, TIMP-1, ColⅠ, Col Ⅲ and ColⅤ in the airway were examined by immunocytochemical methods. During the course of airway remodeling, the dynamic changes of model rats were observed at different time points (2, 4, 6 and 8 weeks after the activating). Statistical comparison was performed by ANOVA followed by Fisher LSD test.Results: (1) Histologic examination showed eosinophil infiltration within the airway walls, epithelial damage, excessive mucus in the lumen and edema in the submucosa of the airways in model rats, and that the collagen deposition increased accompanied by increasing of TIMP-1. In the model rats, MMP-9 increased at the time point of 2 weeks, but it decreased in the late stage (8 weeks after activating) of airway remodeling. And the level of TIMP-1 was far higher than MMP-9 at the time point of 8 weeks. (2) Zhichuan Capsule could down-regulate the level of TIMP-1 in the airway wall, as well as the thickness of airway wall and the collagen deposition. And there were progressing effects when it was used together with dexameson.Conclusion: (1) The early increase of MMP-9 is a key point to start remodeling; and the increase of TIMP-1 in the late stage, which inhibits collagenase activity, may play an important role in developing airway fibrosis. Imbalance between MMP-9 and TIMP-1 is a marker of airway remodeling. (2) Zhichuan Capsule can decrease the deposition of collagen and suppress the airway remodeling by inhibiting the TIMP-1 expression.

Key words: asthma, matrix metalloproteinase, Zhichuan Capsule, airway remodeling, models, rats

CLC Number: 

  • R289.5

Tab 1

MMP-9 and TIMP-1 expression in airway of experimental rats($\bar{x}$±s)"

Group n MMP-9 expression TIMP-1 expression
Ratio of positive area (%) Staining intensity Ratio of positive area (%) Staining intensity
Normal control
2 weeks after activating 4 2.39±0.87 5.50±0.19
 2.61±0.25 7.16±1.03
4 weeks after activating 4 2.64±0.43 6.50±0.33
 2.37±0.22 7.33±0.72
6 weeks after activating 4 2.34±0.21 6.33±0.98
 2.60±0.21 7.36±1.41
8 weeks after activating 4 2.84±0.47 6.16±0.89
 2.38±0.27 7.25±0.83
Model
2 weeks after activating 8 16.49±3.61* 13.46±1.17*
 10.58±1.78* 17.12±1.32*
4 weeks after activating 8 26.70±3.23*Δ 19.04±1.21*Δ
 26.31±3.51*Δ 21.75±1.09*Δ
6 weeks after activating 8 33.72±1.12*Δ 24.54±0.62*Δ
 34.38±1.73*Δ 25.29±1.33*Δ
8 weeks after activating 8 16.72±2.26* 10.96±0.83*
 40.39±1.26*ΔΔ 31.21±1.53*ΔΔ

Tab 2

Thickness and area of airway wall of rats in different groups（$\bar{x}$±s, % ）"

Group n Thickness (d/Pi) Area (WA/Pi2 )
Normal control 8 3.28±0.35 2.40±0.37
Model 8 9.66±1.11* 8.42±1.11*
Zhichuan Capsule treated 8 4.86±0.69*▲ 4.01±0.97*▲
Dexameson treated 8 5.15±0.91*▲ 4.48±0.78*▲
Zhichuan Capsule and dexameson treated 8 4.72±1.08*▲ 4.54±2.22*▲

Tab 3

Collagen expression (ratio of positive area) in airway of rats in different groups（$\bar{x}$±s, % ）"

Group n Collagen typeⅠ Collagen type Ⅲ Collagen type Ⅴ
Normal control 8 10.95±0.49 14.24±0.92 8.89±0.77
Model 8 37.24±1.58* 42.98±1.59* 43.84±2.09*
Zhichuan Capsule treated 8 13.53±0.85*▲□ 23.39±0.71*▲□■ 21.89±0.93*▲□■
Dexameson treated 8 16.14±1.66*▲■ 27.89±0.63*▲■ 24.52±1.07*▲■
Zhichuan Capsule and dexameson treated 8 14.27±0.80*▲□ 19.89±1.04*▲□ 19.06±0.72*▲□

Tab 4

TIMP-1 expression in airway of rats in different groups（$\bar{x}$±s ）"

Group n TIMP-1 expression
Ratio of positive area (%) Staining intensity
Normal control 8 2.38±0.27 7.25±0.83
Model 8 40.38±1.26* 31.20±1.53*
Zhichuan Capsule treated 8 15.08±0.95*▲□■ 15.45±0.87*▲□■
Dexameson treated 8 22.46±1.14*▲■ 16.91±0.58*▲■
Zhichuan Capsule and dexameson treated 8 10.78±2.05*▲□ 13.71±0.65*▲□
[1] 王丽新, 吴银根 . 实验性哮喘大鼠气道重塑的形态学变化[J]. 中西医结合学报, 2003,1(1):62-65
Wang LX, Wu YG . Morphological changes following airway remodeling in asthmatic rats[J]. Zhong Xi Yi Jie He Xue Bao, 2003,1(1):62-65
[2] Salmon M, Walsh DA, Koto H , et al. Repeated allergen exposure of sensitized Brown-Norway rats induces airway cell DNA synjournal and remodeling[J]. Eur Respir J, 1999,14(3):633-641
doi: 10.1034/j.1399-3003.1999.14c25.x
[3] Palmans E, Kips JC, Pauwels RA . Prolonged allergen exposure induces structural airway changes in sensitized rats[J]. Am J Respir Crit Care Med, 2000,161(2):627-635
doi: 10.1164/ajrccm.161.2.9902094 pmid: 10673209
[4] 陈奇 . 中药药理研究方法学(第1版)[M]. 北京: 人民卫生出版社, 1994,( 第1版):33-34
[5] James AL, Hogg JC, Dunn LA , et al. The use of the internal perimeter to compare airway size and to calculate smooth muscle shortening[J]. Am Rev Respir Dis, 1988,138(1):136-139
doi: 10.1164/ajrccm/138.1.136
[6] Wiggs BR, Bosken C, Pare PD , et al. A model of airway narrowing in asthma and in chronic obstructive pulmonary disease[J]. Am Rev Respir Dis, 1992,145(6):1251-1258
doi: 10.1164/ajrccm/145.6.1251 pmid: 1595987
[7] Fish JE, Peters SP . Airway remodeling and persistent airway obstruction in asthma[J]. J Allergy Clin Immunol, 1999,104(3 Pt 1):509-516
doi: 10.1016/S0091-6749(99)70315-5 pmid: 10482819
[8] Vignola AM, Riccobono L, Mirabella A , et al. Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis[J]. Am J Respir Crit Care Med, 1998,158(6):1945-1950
doi: 10.1164/ajrccm.158.6.9803014
[9] Bosse M, Chakir J, Rouabhia M , et al. Serum matrix metalloproteinase-9∶Tissue inhibitor of metalloproteinase-1 ratio correlates with steroid responsiveness in moderate to severe asthma[J]. Am J Respir Crit Care Med, 1999,159(2):596-602
doi: 10.1164/ajrccm.159.2.9802045
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