[Effects of Fuzheng Huayu recipe on MMP-2 activity and type IV collagen expression at fibrotic lung].
OBJECTIVE
To study the mechanism of Fuzheng Huayu (FZHY) recipe against pulmonary fibrosis relating to MMP-2 activity and type IV collagen expression at lung tissue.


METHODS
The pulmonary fibrosis model was induced by intratracheal instillation with bleomycin once in rats. The models were divided into 3 groups: model control, FZHY recipe treated, and methylprednisolone (Solu-Medrol) treated group, each group was of 14 model rats. Normal control group with 10 rats was intoxicated with the same amount of saline. From the second day of intoxication, FZHY recipe treated group orally took FZHY recipe at the dosage of 4.6 g x kg(-1) rat wt, methylprednisolone treated group received intraperitoneal injection with 15 mg x kg(-1) rat wt of methylprednisolone, while model and normal controls took the same volume of saline, 1 time each day and lasting for 4 weeks. Lung and body weights were weighed and the lung/body ratio was calculated. Collagens deposition was check with Masson stain, and lung hydroxyproline (Hyp) content was assayed with Jamall's method. Protein expressions of MMP-2/9 and type IV collagen at lung tissue were analyzed with Western blot and of MMP-2/9 activities by gelatin zymography.


RESULTS
Compared to normal rats, the model control rats had a high lung/body ratio, remarkable collagen deposition, increased Hyp content and the expressions of type IV collagen, MMP-2 and MMP-9 protein at lung tissue, increased MMP-2 activity, in particular active MMP-2 activity, but decreased MMP-9 activity. Compared to model control, FZHY recipe and methylprednisolone obviously attenuated pulmonary collagen deposition, decreased lung/body ratio and Hyp content, downregulated MMP-2 protein expression and activity, in particular active MMP-2 activity, and FZHU recipe had some better actions than methylprednisolone on lung/body ratio, type IV collagen expression and active MMP-2 activity. But both drug groups had no influence on MMP-9 protein expression and activity.


CONCLUSIONS
FZHY recipe has a good action against experimental pulmonary fibrosis and its mechanisms are associated with the inhibition of MMP-2 protein and activity, and with the inhibition of over expression of type IV collagen at lung tissue.
Tan
Shan-Zhong
SZ
Shuguang Hospitol, Shanghai University of Traditional Chinese Medicine, Shanghai 200021, China.
Liu
Cheng-Hai
CH
Zhang
Wei
W
Lu
Xiong
X
Ye
Wei-Cheng
WC
Cai
Zhen-Zhen
ZZ
Liu
Ping
P
D000818:Animals; D001761:Bleomycin; D024141:Collagen Type IV / Q000378:metabolism*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D024141:Collagen Type IV; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D001761:Bleomycin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D006909:Hydroxyproline