The Remoding And Regulation Mechanism About Extracellular Matrix Of Dilated Cardiomyopathy Diease

PURPOSES: To research the effect and significance about MMPs-2 and TIMPs-1 in the model of DCM rats. To investigate the expression of MMP-2,TIMP-1 and collagen fiber during the course of DCM treated with ACEI and without. To explore the the relation between MMPs and PICP, PⅢNP.METHODS: 60 SD rats were divided randomly into two groups: normal control group, the DCM group, the DCM treated with adriamycin intraperitoneally 2.0 mg/kg·week for 8 weeks to estabilsh DCM model. The normal control group was intravitreous injected with normal saline. Transthoracic echocardiography was performed in the DCM group and control guoup rats.DCM who were achieve standard were divided randomly into three groups:(1)A group:the rats who were administered captopril by gavage at a dose of 50mg/kg·d for 3 weeks (2)B group: the rats who were administered captopril by gavage at a dose of 25 mg/kg·d for 3 weeks (3)C group(DCM control group).HE stain was used to observe the change of the Histopathological characteristics . The semiquantitative analysis was used to evaluate the CVF.The expression of MMP-2 and TIMP-1 were quailtative and semiquantitative analysised with immunohistochemistry and RT-PCR .The qualitative analysis was used to evaluate the PICP and PⅢNP in blood plasm.RESULTS:1 Living condition of rats: the normal control group were all survival;the DCM group has been died four rats.2 Compared with the normol control group, venticular interior diameter was enlarge. LVED and LVES were increased significantly(P < 0.05),whereas the FS and EF were decreased(P < 0.05).3 Pathological examination demonstrated that the cardiac muscular tissue of the DCM group were harmed , which characteristic were consistented with dilated cardio- myopathy in the human patients.Compare with the normol group,DCM group's Van Gien stain display that CVF was increased significantly(P < 0.05). Compare with the C group,the A and B group's Van Gien stain display that CVF was decreased significantly (P < 0.05).4 Immunohistochemistry showed that the expression of MMP-2 and TIMP-1 were mainly located in the endochylema and extracellular matrix.The expression of MMP-2 in the normal group,the A and B group were weak at all time. The expression of MMP- 2 in the C group was stronger then normal group (P <0.01). The differences were statistical significance as compared with the A group and the C group (P <0.01). The expression of MMP-2 in the B group was weaker then the C group (P <0.05). The expression of TIMP-1 in the DCM group was weaker then normal group (P<0.01). The differences were statistical significance as compared with the A group and the C group (P <0.01). The differences were statistical significance as compared with the B group and the C group (P <0.05).5 RT-PCR showed that the expression of MMP-2 mRNA in the C group was stronger then the normal group (P<0.01). The differences were statistical significance decrease as compared with the A group and the C group (P <0.01). The expression of MMP-2 in the B group was weaker then the C group (P <0.05).The expression of TIMP-1mRNA in the DCM group was weaker then normal group (P<0.05). The differences were statistical significance as compared with the A group and the C group (P <0.05). There was no statistical significance as compared with the B group and the C group (P﹥0.05).6 ELISA showede that PICP and PⅢNP in blood plasm of the DCM group was increased significantly (P<0.01). The differences were statistical significance as compared with the A,B group and the C group (P <0.01).CONCLUSION: MMP and TIMP involved in the course of the remoding about extra- cellular matrix in dilated cardiomyopathy diease. The higher rate of MMP-2/ TIMP-1 can promote the collegen proliferation and effect the level of myocardial fibrosis.The concentration of PICP and PⅢNP in blood plasm is correlated to the myo- cardial fibrosis .Captopril may be reduced the expression of MMP-2 and up-regulation the level of TIMP-1,then the effect of degradation ECM about MMP-2 can be relief. Captopril played an important role in the treatment of the remoding about extracellular matrix in dilated cardiomyopathy diease .