Effect of Apocynin via TGF-β1/Smad signaling pathway on lipopolysaccharide induced myocardial fibrosis in mice and its effect on ColⅠa1 and ColⅢa1

Zhang Zhongfeng; Liu Peng; Yuan Jianhua

doi:10.3969/j.issn.1674-4055.2019.02.27

Abstract：Objective To investigate the effect of Apocynin on myocardial fibrosis (MF) mice and its effects on ColⅠa1 and ColⅢa1 through TGF-β1/Smad signaling pathway. Methods Forty C57BL/6 male mice were randomly divided into normal control group, Apocynin control group, MF model group and Apocynin intervention group (n=10). The myocardial fibrosis model was established by intraperitoneal injection of LPS (10 mg/kg) once a week for 4 weeks. Apocynin (10 mg/kg) was injected intraperitoneally once a week for 4 weeks in the Apocynin intervention group at 0.5 h before LPS (10 mg/kg) treatment. After each group of mice was sacrificed at the end of the 4th week after cervical dislocation, myocardial fibrosis was detected by Sirius Red staining. The expression of TGF-β1, Smad2/3, and p-Smad 2/3 in myocardial tissue of each group were detected by immunohistochemistry. The relative protein expression was detected by Western blotting. The expression of ColⅠa1 and ColⅢa1 protein in myocardial tissue was detected by Western blot. Results There was no significant difference in the collagen area fraction of TGF-β1, Smad2/3, p-Smad2/3 protein and the expression of fibrotic factors ColⅠa1 and ColⅢa1 between the Apocynin control group and the normal control group (P>0.05). Compared with the normal control group, the collagen area fraction and the expression levels of TGF-β1, Smad2/3, and p-Smad2/3 proteins and the expression of the fibrogenic factors ColⅠa1 and ColⅢa1 in the MF model group were significantly increased (P<0.01). Compared with the MF model group, the collagen area fraction and the expression of TGF-β1, Smad2/3, p-Smad2/3 protein and the expression of the fibrogenic factors ColⅠa1 and ColIIIa1 were significantly decreased in the Apocynin intervention group (P<0.01). Conclusion Apocynin mediated the down-regulation of the fibrogenic factors ColⅠa1 and ColⅢa1 through the TGF-β1/Smad signaling pathway, thereby reducing LPS-induced myocardial fibrosis in mice.