五甲基槲皮素对血管紧张素Ⅱ致大鼠心肌纤维化的作用

目的研究五甲基槲皮素(PMQ)对血管紧张素Ⅱ(AngⅡ)所诱导的大鼠心肌间质纤维化的作用及其机制。方法SD大鼠30只随机分为5组,试验持续21 d。①空白组:每晨生理盐水灌胃;②PMQ组:每晨PMQ 50 mg.kg-1灌胃;③AngⅡ组:于d 15开始皮下注射AngⅡ288μg.kg-1.d-1;④PMQ+AngⅡ组:PMQ和AngⅡ处理同前;⑤溶剂+AngⅡ组:每晨溶剂灌胃,AngⅡ处理同前。d 22处死大鼠,测量心肌羟脯氨酸含量,SOD活力、MDA含量,RT-PCR检测collagenⅠ、collagenⅢ及NADPH oxidase亚单位Nox2和p47phoxmRNA的表达,免疫组化测collagenⅠ、colla-genⅢ容积分数(CVF)及其比值CVFⅠ/CVFⅢ。结果AngⅡ能明显提高大鼠心肌羟脯氨酸含量,上调collagenⅠ、col-lagenⅢ及NADPHoxidase亚单位Nox2和p47phox的mRNA表达,增加collagenⅠ、Ⅲ容积分数及CVFⅠ/CVFⅢ比值,并降低心肌SOD活力、增加MDA含量。PMQ能明显抑制AngⅡ引起的上述改变。结论PMQ能对抗AngⅡ引起的心肌间质纤维化,此效应可能与其抗氧化及下调NADPH oxidasemRNA表达有关。

3,3′,4′,5,7-Pentamethylquercetin reduces cardiac fibrosis in AngiotensinⅡ-infused rats

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 each:① 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 μg·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.