Matrine Prevents Bleomycin-induced Pulmonary Fibrosis In Rat By Down-regulation Of MMP-2 And MMP-9

Objective: In the present study,with the regulation on MMP2 and MMP-9 of matrine,we will investigate the anti-fibrotic effects and conceivable mechanisms of matrine on blemycin-induced lung fibrosis in rats.Methods:Sixty healthy male SD rats were randomly divided into four groups:control group(group A),bleomycin group(group B),matrine50 mg treatment group(group C), matrine100 mg treatment group(group D).Bleomycin was intratracheally administrated at a dose of5mg/kg for once to make the model of pulmonary fibrosis in all groups except A which was given equivalent volume of normal saline in the same way. matrine was administrated by oral at a dose of 50mg/kg and100mg/kg from day1 to 28 to the rats respectively in the groupC and D.The equivalent volume of normal saline was administrated in the group A and B.All animals were sacrificed on day7, 14 and 28,5 rats each time,and the lung specimens were harvested for HE stain and Masson stain;The expressions of MMP-2 and MMP-9 were analyzed by means of immunohistochemistry(PV)and RT-PCR respectively.Results:(1)There were neither Widened alveolar septumnor Interstitial inflammation and fibrotic change in group A showed by HE and Masson staining.In group B, the alveolar structure is disrupted, a large number of inflammatory cells infiltrated into alveolar space, small fibrotic areas appeared on the 7th day. on the 14 th day,more alveolar structure is disrupted and inflammatory cells infiltrated into alveolar space are still visible;collagen deposition and fibrosis were aggravated.But on the 28 th day,the normal alveolar structure almost disappear,a large number of collagen deposition and fibrosis area instead.The degree of pulmonary alveolitis and fibrosis in group C and D was improved than group B.(2)Immunohistochemistry(PV)and RT-PCR results:In group A,both of the mmp-2 and mmp-9 are expressed weakly;In group B,the express of mmp-2 increased on the 7th day,reaching the peak level on the14 th day and then decreased,but still remained at significantly higher levels till the 28 th day,compared to the group A(p <0.05); However,the express of mmp-9 increased rapidly and reach the peak level on the 7th day,decreased gradually and returned to normol level on the 28 th day,which was on statistically significant compared to the group A(p>0.05).Increased expression of mmp-2 and mmp-9 was inhibited in group C and D,but the change of group D was more significant than group C(p <0.05).Conclusion:(1)Matrine can prevent bleomycin-induced pulmonary fibrosis in rats.(2)The possible mechanisms of Matrine on lung fibrosis may be associated with inhibiting the expression of MMP-2 and MMP-9.