3,3′,4′,5,7-Pentamethylquercetin reduces cardiac fibrosis in AngiotensinⅡ-infused rats / 中国药理学通报

ABSTRACT

Aim To investigate the effect of 3,3′,4′,5,7-pentamethylquercetin(PMQ) on angiotensin Ⅱ(AngⅡ) induced cardiac fibrosis.Methods Thirty rats were randomly assigned to the 5 groups,6 each① control group Saline was administrated daily via gavage for 21 days;② PMQ group PMQ(50 mg?kg-1) was administrated daily via gavage for 21 days;③ AngⅡ group AngⅡ(288 ?g?kg-1?d-1)was injected subcutaneously daily from the 15 th day;④ PMQ+ AngⅡ group PMQ and AngⅡ were administrated as above;and ⑤ solvent+ AngⅡ group Solvent and AngⅡ were administrated as above.After the rats were euthanized on the 22 nd day,the myocardial hydroxyproline content,SOD activity and MDA content were measured,and the expression of collagenⅠ,collagenⅢ,and NADPH oxidase subunits Nox2 and p47phox mRNA were determined by real time-PCR.Collagen volume fraction(CVF) Ⅰand Ⅲ were detected by immunohistochemistry,and CVFⅠ/CVFⅢ was calculated.Results PMQ reduced cardiac fibrosis in AngⅡ induced hypertension rats by decreasing the myocardial hydroxyproline content,downregulating the expression of collagenⅠand collagenⅢ mRNA,and decreasing CVFⅠ,CVFⅠ/CVFⅢ.PMQ exerted antioxidant function by increasing SOD activity and decreasing MDA content and reducing the mRNA expression of NADPH oxidase subunits Nox2 and p47phox.Conclusion PMQ could reduce cardiac fibrosis,which may result from the inhibition of the expression of NADPH oxidase.The results suggest that PMQ may represent a promising therapeutic approach for CHF treatment.