Effects Of Omega-3 Long-chain Unsaturated Fatty Acids On Myocardial Extracellular Matrix Remodeling In Rats With Cardiac Hypertrophy

Objective To investigate the effect of omega-3 long-chain unsaturated fatty acids on remodeling of extracellular matrix in cardiac hypertrophy rats after abdominal aortic constriction.Methods Forty male Sprague-Dawley rats were randomly divided into two groups:the sham operation group(Sham group)and the cardiac hypertrophy group(CH group).Abdominal aortic coarctation in CH group.One week after operation,the cardiac hypertrophy group was randomly divided into three groups: the abdominal aortic constriction group(AAC group),the abdominal aortic constriction + n-3 PUFAs low dose group(AAC+n-3L group),the abdominal aortic constriction + n-3 PUFAs High dose group(AAC+n-3H group).The AAC+n-3L and AAC+n-3H groups were given 400mg/kg.d and 1000 mg/kg.d n-3 PUFAs respectively,while the Sham group and the AAC group were given an equal volume of normal saline.After 8 weeks,all the rats were sacrificed.The left ventricular mass index(LVW / BW)and heart mass index(HW/BW)were measured.HE staining and Masson staining were performed on the myocardial tissue.Serum was detected for hydroxyproline.The content of metalloproteinase-9,metalloproteinase inhibitor-1 and fibronectin in myocardial tissue was analyzed by Western blot.Results 1)Compared with the Sham group,the left ventricular mass index,cardiac massindex,and hydroxyproline content in the AAC group,AAC+n-3L group,and AAC+n-3H group were significantly increased(P<0.05).Pathological staining showed cardiomyocytes hypertrophy,and collagen fibers,collagen volume fraction also increased.Collagen fibers increased mainly with type I and type III collagen fibers.The expression of metal matrix protease-9 and fibronectin were alleviated,while metal matrix protease inhibitor-1 were lower(P<0.05).2)Compared with the AAC group,the left ventricular mass index,cardiac mass index,and hydroxyproline in the AAC+n-3L group and the AAC+n-3H group decreased(P<0.05).Pathological staining showed that the cardiomyocytes,collagen volume fraction,total collagen content and type I collagen fiber content decreased.The expression of metal matrix protease-9 and fibronectin expression were alleviated,while metalloproteinase inhibitor-1 expression were lower(P<0.05).3)Compared with AAC+n-3L group,left ventricular mass index,cardiac mass index and hydroxyproline content in AAC+n-3H group were decreased(P<0.05).Pathological staining showed decrease of myocardial cells,collagen volume fraction,total collagen content,type I collagen fiber content,the expression of metalloproteinase-9 and fibronectin,while the expression of metalloproteinase inhibitor-1 were lower(P<0.05).Conclusions 1.The model of cardiac hypertrophy can be successfully replicated by abdominal aortic coarctation.2.n-3 PUFAs have protective effects on cardiac hypertrophy and may be dose related.3.The mechanism of n-3 PUFAs to improve cardiac hypertrophy may be related to inhibition of overexpression of metalloproteinase-9 and fibronectin,up-regulation of metalloproteinaseinhibitor-1 expression,and affecting myocardial extracellular matrix remodeling.