Effects Of Bufeikangxian Decoction To Expression Of MMP-9 And TIMP-1 In Rats Of Pulmonary Fibrosis

Objective: To observe Bufeikangxian decoction's effects to expression of matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloproteinase-l(TIMP-l) in bleomycin-induced pulmonary fibrosis in rats model. To detect the mechanism of its' healing pulmonary fibrosis.Methods: 60 male Wistar rats were randomly divided into 4 groups: bleomycin group, control group, bufikangxian decoction group and prednisone group. Dynamic changes of the pathomorphism and the contents of Hydroxyproline(HYP) of rats' lung, MMP-9 and TIMP-1 protein expression was observed respectively in each group.Results: (1)Histologic findings of Bleomycin group showed that obvious alveolitis changes was observed at 7d, fibrotic changes emerged at 14d and became severe at 28d. After bufeikangxian decoction or prednisone administration, the alveolitis and fibrotic changes were milder in degree. Significant differences were found compared with bleomycin group (P<0.01). (2)After Bleomycin administration, significant increase in HYP of the lung was detected. By healing with bufeikangxian decoction or prednisone, obvious decrease was found compared with bleomycin group (P<0.05 or P<0.01). (3) A little MMP-9 protein expressed in the control group. Strong MMP-9 protein expression of bleomycin group was detected at 7d. Then it was decreased at 14d and 28d, but superior to that of the control group. After bufeikangxian decoction or prednisone treatment, MMP-9 protein expressed weakly compared with bleomycin group at 7d(P<0.05) and continuously decreased at 14d and 28d but there wasn't significant difference compared with bleomycin group (P>0.05).(4) There was a little TIMP-1 protein expression of the control group. TIMP-1 protein expression of bleomycin group was detected at 7d. Then it was increased continuously, significant difference was found compare with the control group(P<0.01). After bufeikangxian decoction or prednisone administration, TIMP-1 protein expressed significantly decreased compared with bleomycin group at 7d, 14d and 28d (P<0.05 or P<0.01). 'Conclusions: (1) Both MMP-9 and TIMP-1 expressed highly in early period of IPF, but with MMP-9 increases for lord. In later period of IPF TIMP-1 keeps on high expression, hinting that in earlier period MMP-9 expressed increase and MMP-9/TIMP-1 diminished in later period caused apposition of ECM. (2)The study shows that Bufeikangxian decoction has the effects of antifibrosis. The mechanism was possibly as it can decrease the expression of MMP-9 at alveolitis period and mainly inhibit the expression of TIMP-1 protein at later IPF period so that it can keep the balance between MMP-9 and TIMP-1 to regulate ECM metabolism.