Lee Kyung Hye, Kwon Sung Jin, Woo Jong-Shin, Lee Gi-Ja, Lee So-Ra, Jang Hyun-Hee, Kim Hyun Soo, Kim Jung Wook, Park Hun Kuk, Cho Kyu Seok, Kim Weon
Cardiovascular Division, Department of Internal Medicine, Kyung Hee University, Seoul, Korea.
Clin Exp Pharmacol Physiol. 2014 Oct;41(10):763-8. doi: 10.1111/1440-1681.12290.
Sildenafil exerts cardioprotective effects by activating the opening of mitochondrial ATP-sensitive potassium channels to attenuate ischaemia-reperfusion (IR) injury. In the present study, we used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties to assess sildenafil-mediated cardioprotection in a rat myocardial infarction model. To investigate the cardioprotective effects of sildenafil, we used an in vivo Sprague-Dawley rat model of IR. Rats were randomly divided into three groups: (i) sham-operated rats (control; n = 5); (ii) IR-injured rats treated with vehicle (normal saline; IR; n = 10); and (iii) IR-injured rats treated with 0.75 mg/kg, i.p., sildenafil (IR + Sil; n = 10). Morphological and mechanical changes to mitochondria were analysed by AFM. Infarct areas were significantly reduced in sildenafil-treated rats (7.8 ± 3.9% vs 20.4 ± 7.0% in the sildenafil-treated and untreated IR groups, respectively; relative reduction 62%; P < 0.001). Analysis of mitochondria by AFM showed that IR injury significantly increased the areas of isolated mitochondria compared with control (24 150 ± 18 289 vs 1495 ± 1139 nm(2) , respectively; P < 0.001), indicative of mitochondrial swelling. Pretreatment with sildenafil before IR injury reduced the mitochondrial areas (7428 ± 3682 nm(2) ; P < 0.001; relative reduction 69.2% compared with the IR group) and ameliorated the adhesion force of mitochondrial surfaces. Together, these results suggest that sildenafil has cardioprotective effects against IR injury in a rat model by improving the morphological and mechanical characteristics of mitochondria.
西地那非通过激活线粒体ATP敏感性钾通道的开放来减轻缺血再灌注（IR）损伤，从而发挥心脏保护作用。在本研究中，我们使用原子力显微镜（AFM）来研究线粒体形态和特性的变化，以评估西地那非在大鼠心肌梗死模型中介导的心脏保护作用。为了研究西地那非的心脏保护作用，我们使用了IR的体内Sprague-Dawley大鼠模型。大鼠被随机分为三组：（i）假手术大鼠（对照组；n = 5）；（ii）接受载体（生理盐水）治疗的IR损伤大鼠（IR；n = 10）；和（iii）腹腔注射0.75 mg/kg西地那非治疗的IR损伤大鼠（IR + Sil；n = 10）。通过AFM分析线粒体的形态和力学变化。西地那非治疗的大鼠梗死面积显著减小（分别为7.8±3.9%和20.4±7.0%，西地那非治疗组和未治疗的IR组；相对减少62%；P < 0.001）。通过AFM对线粒体进行分析表明，与对照组相比，IR损伤显著增加了分离线粒体的面积（分别为24 150±18 289和1495±1139 nm²；P < 0.001），表明线粒体肿胀。IR损伤前用西地那非预处理可减小线粒体面积（7428±3682 nm²；P < 0.001；与IR组相比相对减少69.2%），并改善线粒体表面的粘附力。总之，这些结果表明，西地那非通过改善线粒体的形态和力学特性，对大鼠模型中的IR损伤具有心脏保护作用。
