The effect of carvedilol on TGF-beta-Smad pathways in myocardial fibrosis (MF) induced by Isoproterenol
2013, 33(11):
1475-1479.
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Objective To investigate the effect of TGF-beta-Smad signaling pathway in cardiac fibrosis induced by isoproterenol（ISO）in rats and the intervention mechanism of carvedilol. Methods Thirty male Sprague-Dawley rats were randomly divided into ISO model group（M group），carvedilol treatment group (T group)and control group(C group). Cardiac fibrosis models were induced in M group and T group by subcutaneous injection of ISO（5mg/(kg?d)for 10 days）. Rats of C group were injected normal saline（5ml/(kg?d)for 10days）instead, after 10 days, rats of T group were fed carvedilol（10mg/(kg?d)） for 4 weeks. Rats of M and C group were
fed normal saline 10ml/(kg?d) for 4 weeks instead, after 4 weeks,all the rats were killed to measure the CWI. The pathological changes of myocardial tissue were observed by HE staining and the changes of collagen fiber hyperplasia were detected through Massion staining. The mRNA expression level of TGF-β1, Smad3 and Smad7 were determined by RT-PCR. The protein level of TGF-β1, Smad3 and Smad7 were detected by immunohistochemistry. Results Pathology changes were observed by light microscope : There were changes in M group including cardiac muscle cell hypertrophy, prolongation,fibrosis and calcification presented between the cells, in addition, myocardial collagen fibers increased significantly in masson dyeing cells in M group than that in T group and C group. T group heart muscle cells could be seen parallelism arrange. There was small amounts of areolar tissue in cellular stroma. Between the cells collagen fibers could be found, but the amount and area was decreased markedly. Compared with those of C group, all of the CWI, the expression levers of TGF-β1 mRNA, the Smad3 mRNA, TGF-β1 protein, and the Smad3 protein were significantly increased(all P<0.01), and the expression levers of Smad7 mRNA and the Smad7 protein were significantly lower in M group (P<0.01;P<0.05). However, the expression levers of TGF-β1 mRNA, the Smad3 mRNA, TGF-β1 protein, and the Smad3 protein were much lower(P<0.01;P<0.05), and the expression levers of Smad7 mRNA and the Smad7 protein were significantly higher in T group than M group(P<0.01;P<0.05). Conclusion TGF-beta-Smad signaling pathway may play an important role in myocardial fibrosis induced by ISO, and carvedilol can improve the pathological changes, which might be associated with the inhibition of TGF-beta-Smad signaling pathway.
