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阿托伐他汀对大鼠急性心肌梗死后心功能及转化生长因子-β1信号通路的影响

[Effect of atorvastatin on cardiac function and TGF-β1 signaling pathway after acute myocardial infarction in rats].

作者信息

Song Yuanbin, Qiu Ruofeng, Kuang Jian, Huang Yuli, Cai Anping, Dai Gang, Mai Weiyi

机构信息

Department of Cardiology, Sun Yat-sen University, Guangzhou, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2012 Feb;32(2):202-6.

Abstract

OBJECTIVE

To investigate the effect of atorvastatin on cardiac remodeling and function after acute myocardial infarction (AMI) in rats and whether this effect is mediated by transforming growth factor-β1 (TGF-β1) signaling pathway.

METHODS

AMI was induced by left coronary artery ligation in 64 male Sprague-Dawley rats, and 45 surviving rats were randomized into control group (n=15), low-dose atorvastatin group (10 mg/kg, n=15) and high-dose atorvastatin group (20 mg/kg, n=15). Similar surgical procedure was performed in sham-operated rats (n=15) without coronary ligation. Atorvastatin was given daily by gavage from the first day after AMI. Eight weeks later, the cardiac function, left ventricular weight/body mass index (LVMI), collagen volume fraction (CVF), and the expressions of TGF-β1 and Smad2 were compared between the groups.

RESULTS

AMI caused significantly reduced cardiac function, increased LVMI and CVF, and upregulated expressions of TGF-β1 and Smad2 mRNA and proteins in the control group (P<0.05). The cardiac function, LVMI, and CVF were improved by atorvastatin, which also down-regulated the expressions of TGF-β1 and Smad2 (P<0.05), and the effects were more prominent in high-dose atorvastatin group (P<0.05).

CONCLUSION

Atorvastatin can dose-dependently improve cardiac remodeling and function after AMI in rats, which is mediated by regulating the activity of TGF-β1/Smad2 signaling pathway.

摘要

目的

探讨阿托伐他汀对大鼠急性心肌梗死(AMI)后心脏重构及功能的影响,以及该作用是否通过转化生长因子-β1(TGF-β1)信号通路介导。

方法

采用左冠状动脉结扎法诱导64只雄性Sprague-Dawley大鼠发生AMI,45只存活大鼠随机分为对照组(n = 15)、低剂量阿托伐他汀组(10 mg/kg,n = 15)和高剂量阿托伐他汀组(20 mg/kg,n = 15)。对15只假手术大鼠进行类似手术操作,但不进行冠状动脉结扎。自AMI后第一天起每天经口灌胃给予阿托伐他汀。8周后,比较各组心脏功能、左心室重量/体重指数(LVMI)、胶原容积分数(CVF)以及TGF-β1和Smad2的表达。

结果

对照组中,AMI导致心脏功能显著降低、LVMI和CVF增加,TGF-β1和Smad2 mRNA及蛋白表达上调(P < 0.05)。阿托伐他汀改善了心脏功能、LVMI和CVF,同时下调了TGF-β1和Smad2的表达(P < 0.05),且在高剂量阿托伐他汀组中作用更显著(P < 0. – 05)。

结论

阿托伐他汀可剂量依赖性地改善大鼠AMI后的心脏重构及功能,其作用通过调节TGF-β1/Smad2信号通路的活性介导。

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