Rose Madhankumar, Balakumar Pitchai, Singh Manjeet
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
Pharmacology. 2007;80(2-3):177-84. doi: 10.1159/000103917. Epub 2007 Jun 15.
The present study has been designed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor (PPAR)alpha agonist, rosiglitazone, a PPARgamma agonist and the combination of both fenofibrate and rosiglitazone in partial abdominal aortic constriction (PAAC)-induced pathological cardiac hypertrophy in rats. Rats were subjected to PAAC for 4 weeks to produce pathological cardiac hypertrophy. The fenofibrate (3 mg/kg day(-1), p.o.), rosiglitazone (3 mg/kg day(-1), p.o.) and the combination of both fenofibrate (3 mg/kg day(-1), p.o.) and rosiglitazone (3 mg/kg day(-1), p.o.) were administered 3 days before PAAC and continued for 4 weeks after PAAC. The development of cardiac hypertrophy was assessed in terms of measuring ratio of left ventricular (LV) weight to body weight (LVW/BW), LV wall thickness (LVWT), LV protein content and LV collagen content. Further, the collagen accumulation in left ventricle was analyzed using picrosirius red staining. Moreover, the cross-sectional area (CSA) of cardiomyocytes was assessed using hematoxylin and eosin staining and measured using a NIH Scion image analyzer. The PAAC produced cardiac hypertrophy by increasing LVW/BW, LVWT, LV protein content, LV collagen content and mean CSA of cardiomyocytes. However, treatment with fenofibrate and rosiglitazone either alone or in combination significantly attenuated PAAC-induced increase in LVW/BW, LVWT, LV protein content, LV collagen content and mean CSA of cardiomyocytes. The combination of fenofibrate and rosiglitazone was more effective in attenuating the PAAC-induced cardiac hypertrophy than either drug alone. Thus, it may be concluded that dual activation of PPARalpha and PPARgamma may provide synergistic benefits in preventing the development of pathological cardiac hypertrophy.
本研究旨在探讨过氧化物酶体增殖物激活受体（PPAR）α激动剂非诺贝特、PPARγ激动剂罗格列酮以及非诺贝特与罗格列酮联合用药对大鼠腹主动脉部分缩窄（PAAC）诱导的病理性心肌肥大的影响。大鼠接受PAAC处理4周以产生病理性心肌肥大。在PAAC前3天给予非诺贝特（3mg/kg·天⁻¹，口服）、罗格列酮（3mg/kg·天⁻¹，口服）以及非诺贝特（3mg/kg·天⁻¹，口服）与罗格列酮（3mg/kg·天⁻¹，口服）的联合用药，并在PAAC后持续给药4周。通过测量左心室（LV）重量与体重之比（LVW/BW）、LV壁厚度（LVWT）、LV蛋白含量和LV胶原蛋白含量来评估心肌肥大的发展。此外，使用苦味酸天狼星红染色分析左心室中的胶原蛋白积累。此外，使用苏木精和伊红染色评估心肌细胞的横截面积（CSA），并使用NIH Scion图像分析仪进行测量。PAAC通过增加LVW/BW、LVWT、LV蛋白含量、LV胶原蛋白含量和心肌细胞平均CSA产生心肌肥大。然而，单独或联合使用非诺贝特和罗格列酮治疗可显著减轻PAAC诱导的LVW/BW、LVWT、LV蛋白含量、LV胶原蛋白含量和心肌细胞平均CSA的增加。非诺贝特和罗格列酮联合用药在减轻PAAC诱导的心肌肥大方面比单独使用任何一种药物更有效。因此，可以得出结论，PPARα和PPARγ的双重激活在预防病理性心肌肥大的发展中可能提供协同益处。
