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实验性诱导心肌坏死中HMG CoA还原酶抑制剂的比较评价:生物化学、形态学和组织学研究。

Comparative evaluation of HMG CoA reductase inhibitors in experimentally-induced myocardial necrosis: Biochemical, morphological and histological studies.

作者信息

Variya Bhavesh C, Patel Snehal S, Trivedi Jinal I, Gandhi Hardik P, Rathod S P

机构信息

Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India.

Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India.

出版信息

Eur J Pharmacol. 2015 Oct 5;764:283-291. doi: 10.1016/j.ejphar.2015.07.024. Epub 2015 Jul 10.

Abstract

The present study was carried out to evaluate the protective effect of different statins on isoproterenol (ISO) induced myocardial necrosis. Atorvastatin, rosuvastatin, fluvastatin, simvastatin and pravastatin (10 mg/kg/day) were administered for 12 weeks. After pretreatment of 12 weeks myocardial necrosis was induced by subsequent injection of ISO (85 mg/kg/day, s.c.) to wistar rats. Serum biochemical parameters like glucose, lipid profile, cardiac markers and transaminases were evaluated. Animals were killed and heart was excised for histopathology and antioxidant study. Statins pretreated rats showed significant protection against ISO induced elevation in serum biochemical parameters and serum level of cardiac marker enzymes and transaminase level as compared to ISO control group. Mild to moderate protection was observed in different statins treated heart in histopathology and TTC stained sections. Result from our study also revealed that statins could efficiently protect against ISO intoxicated myocardial necrosis by impairing membrane bound enzyme integrity and endogenous antioxidant enzyme levels. Amongst all statins used, rosuvastatin and pravastatin were found to have maximum cardio-protective activity against ISO induced myocardial necrosis as compared to other statins.

摘要

本研究旨在评估不同他汀类药物对异丙肾上腺素(ISO)诱导的心肌坏死的保护作用。给予阿托伐他汀、瑞舒伐他汀、氟伐他汀、辛伐他汀和普伐他汀(10毫克/千克/天),持续给药12周。在经过12周的预处理后,通过随后向Wistar大鼠皮下注射ISO(85毫克/千克/天)诱导心肌坏死。评估了血清生化参数,如血糖、血脂谱、心脏标志物和转氨酶。处死动物并取出心脏进行组织病理学和抗氧化研究。与ISO对照组相比,他汀类药物预处理的大鼠对ISO诱导的血清生化参数升高、心脏标志物酶血清水平和转氨酶水平具有显著的保护作用。在组织病理学和TTC染色切片中,不同他汀类药物治疗的心脏观察到轻度至中度的保护作用。我们的研究结果还表明,他汀类药物可通过损害膜结合酶完整性和内源性抗氧化酶水平,有效保护免受ISO中毒引起的心肌坏死。在所有使用的他汀类药物中,与其他他汀类药物相比,发现瑞舒伐他汀和普伐他汀对ISO诱导的心肌坏死具有最大的心脏保护活性。

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