NADPH oxidase inhibitor-apocynin in preventing cardiac fibrosis in mice exposed to subclinical lipopolysaccharide
Objective To investigate the preventive effects of apocynin,an NADPH oxidase inhibitor,on cardiac fibrosis in mice exposed to subclinical lipopolysaccharide.Methods Totally 40 male C57BL/6J mice were divided randomly into 4 groups:control group,apocynin group,LPS group and LPS + apocynin group.LPS was injected intraperitoneally once a week for 4 weeks to mimic cardiac fibrosis in LPS group and LPS + apocynin group.Apocynin was given in apocynin group and LPS + apocynin group,once a week for 4 weeks.Collagen fraction area of the left ventricle was measured with picrosirius red staining.The cardiac expression of fibrosis-related genes was measured by RT-PCR.The subunits gp91 phox and p67phox of NADPH oxidase were analyzed by Western blot,ROS production was determined by DHE staining.Results The cardiac fibrosis of mice occurred after 4 weeks.Compared with control group,the interstitial diffuse fibrous tissue in myocardium,the collagen volume fraction,the mRNA expression of LPS-induced activation of fibrosis-related genes Col Ⅰ a 1,Col Ⅲ a1,MMP2 and MMP9,the expression gp91 phox and p67phox and ROS production in LPS group were increased.Compared with LPS group,apocynin decreased the above indexes significantly (P < 0.05).Conclusion Apocynin can protect against the cardiac fibrosis in mice exposed to subclinical LPS by inhibiting the over-expression of myocardial gp91phox and p67phox.