Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Room No. 4017, Ansari Nagar, New Delhi, 110029, India.
Department of Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, 121001, India.
Mol Cell Biochem. 2018 Dec;449(1-2):185-194. doi: 10.1007/s11010-018-3355-3. Epub 2018 May 14.
Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats. FF, because of its pleiotropic property, could be helpful in reducing inflammation, oxidative stress, and reactive oxygen species. On day 1, MCT (50 mg/kg, s.c.) was given to all the rats in MCT, sildenafil, and FF group except normal control rats. After 3 days of giving MCT, sildenafil (175 µg/kg, orally) and FF (120 mg/kg, orally) were given for 25 days. Echocardiography, hemodynamic parameters, fulton's index, histopathology, oxidative stress parameters, inflammatory markers, Bcl2/Bax gene expression ratio in the right ventricle, and protein expression for NOX-1 in lungs were studied in all the groups. FF has shown to prevent decrease in ratio of pulmonary artery acceleration time to ejection time, increase in ratio of right ventricular outflow tract dimension to aortic outflow dimension, rise in right ventricular systolic pressure, right ventricular hypertrophy, increase in the percentage medial wall thickness (%MWT), increase in oxidative stress and inflammation, increase in NADPH oxidase-1 (NOX-1) expression, and decrease in mRNA expression of Bcl2/Bax ratio caused by MCT. To conclude, FF prevented MCT-induced PH in rats by various mechanisms. It might be helpful in preventing PH in patients who are likely to develop PH.
肺动脉高压（PH）是人类心肺以及多种系统性疾病的一种严重并发症。如果不加以治疗，它会迅速进展并导致死亡。在本研究中，我们研究了过氧化物酶体增殖物激活受体α激动剂非诺贝特（FF）对野百合碱（MCT）诱导的大鼠 PH 的影响。由于其多效性，FF 可能有助于减轻炎症、氧化应激和活性氧。在第 1 天，除正常对照组大鼠外，MCT 组、西地那非组和 FF 组所有大鼠均给予 MCT（50mg/kg，皮下注射）。给予 MCT 3 天后，给予西地那非（175µg/kg，口服）和 FF（120mg/kg，口服）25 天。对所有组的超声心动图、血流动力学参数、富尔顿指数、组织病理学、氧化应激参数、炎症标志物、右心室中 Bax/Bcl2 基因表达比值、肺中 NADPH 氧化酶-1（NOX-1）的蛋白表达进行了研究。FF 可预防 MCT 引起的肺动脉加速时间与射血时间比值降低、右心室流出道与主动脉流出道比值升高、右心室收缩压升高、右心室肥厚、中膜厚度百分比（%MWT）升高、氧化应激和炎症增加、NOX-1 表达增加以及 Bax/Bcl2 比值的 mRNA 表达降低。综上所述，FF 通过多种机制预防 MCT 诱导的大鼠 PH。它可能有助于预防可能发生 PH 的患者的 PH。
