五甲基槲皮素对AngⅡ致心肌肥厚和细胞凋亡的作用

Effects of 3,3′,4′,5,7-Pentamethylquercetin on Cardiac Hypertrophy and Apoptosis in Angiotensin Ⅱ-infused Rats

目的研究五甲基槲皮素(PMQ)对血管紧张素Ⅱ(AngⅡ)致大鼠心肌肥厚和细胞凋亡的作用及机制。方法30只SD大鼠随机分为5组,试验持续21d。①空白组:每晨生理盐水灌胃;②PMQ组:每晨PMQ50mg/kg灌胃;③AngⅡ组:于第15天开始皮下注射AngⅡ288μg/(kg.d);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。于第22天处死大鼠,测量心脏指数、左心指数,心肌超氧化物歧化物(SOD)活力和丙二醛(MDA)含量,实时荧光定量(real time)PCR检测脑钠素(BNP)mRNA的表达,TUNEL法测心肌凋亡,免疫组化测Bax、Bcl-2蛋白的表达。结果PMQ能明显抑制AngⅡ所致的心肌肥厚[左心指数,(2.02±0.16)vs(2.34±0.10)mg/g]及BNP mRNA表达上调;抑制心肌细胞凋亡[凋亡指数,(0.72±0.18)vs(1.28±0.27)%]及凋亡相关蛋白Bax表达[平均吸光度(0.0373±0.0073)vs(0.0540±0.0068)]和Bax/Bcl-2的提高[(0.17±0.03)vs(0.25±0.04)],并降低SOD活力、增加MDA含量。结论PMQ能对抗AngⅡ引起的心肌肥厚及细胞凋亡。此效应可能与其抗氧化作用有关。

Objective The hypothesis that pentamethylquercetin （PMQ） reduces cardiac hypertrophy and myocyte apoptosis was tested in Angiotensin Ⅱ （Ang Ⅱ）-infused rats. Methods Thirty rats were randomly assigned to the 5 groups with 6 rats in each group. （1） control group： Saline gavage was performed daily for 21 days; （2） PMQ group.. PMQ （50 mg/kg） gavage was performed daily for 21 days; （3） Ang Ⅱ group： Ang Ⅱ （288 μg/kg . day） was daily injected subcutaneously from the 15th days （4） PMQ＋Ang Ⅱ group： PMQ gavage and Ang Ⅱ injection were performed as the same as above; and （5） solvent＋Ang Ⅱ group： Solvent gavage was performed daily for 21 days, and Ang Ⅱ injection was performed as the same as above. After the rats were euthanized at 22nd day, the heart weight index （HW/BW） and the left ventricular weight index （LVW/BW） were calculated, SOD activity and MDA content were measured, and the expression of BNP mRNA was detected by real time-PCR. Myocyte apoptosis was examined by TUNEL assay and the expression of Bax and Bcl-2 was determined by immunohistochemistry. Results PMQ reduced cardiac hypertrophy induced by Ang Ⅱ by decreasing the heart weight index, the left ventricular weight index [（2.02±0.16） vs （2.34±0. 10） mg/g] and the expression of BNP mRNA, inhibited myocyte apoptosis [AI, （0.72±0.18） vs （1.28±0.27） %] by reducing the expression of Bax [-（0. 037 3±0. 007 3） vs （0. 054 0） ± 0. 006 8）], Bax/ Bcl-2 [（0. 17±0.03） vs （0.25±0.04）], and had antioxidant function by improving SOD activity and lowering MDA content. Conclusion PMQ reduces cardiac hypertrophy and myocyte apoptosis, which may be related to its antioxidant function. The results suggest that PMQ may represent an attractive therapeutic approach to treat congestive heart failure.