五甲基槲皮素对血管紧张素Ⅱ致大鼠心肌纤维化的作用  

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

作　　者：毛张凡[1] 孙宗全[1] 杜心灵[1] 

机构地区：[1]武汉大学人民医院胸外科,湖北武汉430060

出　　处：《中国药理学通报》2009年第8期1103-1107,共5页Chinese Pharmacological Bulletin

摘　　要：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。Aim To investigate the effect of 3,3＇,4＇,5 , 7 - pentamethylquercetin （ PMQ ） on angiotensin Ⅱ（Ang Ⅱ） induced cardiac fibrosis. Methods Thirty rats were randomly assigned to the 5 groups, 6 each： ①control group： Saline was administrated daily via gavage for 21 days;②PMQ group： PMQ （50 mg·kg^-1） was administrated daily via gavage for 21 days;③Angll group： Angll （288 μg·kg^-1·d^-1）was injected subcutaneously daily from the 15 th day; ④PMQ ＋ Ang Ⅱ group ： PMQ and Ang Ⅱ were administrated as above; and ⑤solvent ＋ Ang Ⅱ group： Solvent and Ang Ⅱ 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 collagen Ⅰ, collagen Ⅲ, and NADPH oxidase subunits Nox2 and p47^phox mRNA were determined by real time-PCR. Collagen volume fraction （CVF） Ⅰ and Ⅲ were detected by immunohistochemistry, and CVF Ⅰ/CVF Ⅱ was calculated. Results PMQ reduced cardiac fibrosis in Ang Ⅱ induced hypertension rats by decreasing the myocardial hydroxyproline content, downregulating the expression of collagen Ⅰ and collagen Ⅱ mRNA, and decreasing CVF Ⅰ, CVF Ⅰ/CVF m. PMQ exerted antioxidant function by increasing SOD activity and decreasing MDA content and reducing the mRNA expression of NADPH oxidase subunits Nox2 and p47^phox. 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.

关 键 词：五甲基槲皮素 血管紧张素Ⅱ 纤维化 心肌重构 NADPH OXIDASE 

分 类 号：R-332[医药卫生] R282.71