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曲美他嗪对心肌病叙利亚仓鼠BIO 14:6的长期治疗

Long-term therapy with trimetazidine in cardiomyopathic Syrian hamster BIO 14:6.

作者信息

D'hahan N, Taouil K, Dassouli A, Morel J E

机构信息

Laboratoire de Biologie, Ecole Centrale de Paris, Châtenay-Malabry, France.

出版信息

Eur J Pharmacol. 1997 Jun 11;328(2-3):163-74. doi: 10.1016/s0014-2999(97)83042-7.

Abstract

The cardiomyopathic Syrian hamster (CMH) of the strain BIO 14:6 is a model for both cardiac and skeletal muscle abnormalities. It has reduced longevity and noticeable hypertrophy of the heart and liver. At 220 days, CMHs display a total Ca2+ overload, 1.3-1.8-fold normal and a cytosolic Ca2+ concentration 2-4-fold higher than normal. Long-term oral treatment (18 mg/kg per day) with trimetazidine (anti-ischaemic drug), from age 30 to 350 days, was more efficient than the standard Ca2+ blocker verapamil. Trimetazidine increased the median survival time of CMH by 57% and the hypertrophy disappeared. The total Ca2+ level in CMHs reverted to that of normal Syrian hamsters (F1B). The cytosolic Ca2+ overload was limited to a factor of approximately 2. Therefore, trimetazidine possesses anti-Ca2+ properties and is effective in increasing survival and decreasing the heart and liver hypertrophy of CMH. This suggests that trimetazidine may be valuable in the prevention of congestive heart failure of similar aetiology.

摘要

BIO 14:6品系的心肌病叙利亚仓鼠(CMH)是一种用于研究心脏和骨骼肌异常的模型。它的寿命缩短,心脏和肝脏明显肥大。在220天时,CMH表现出总Ca2+过载,是正常水平的1.3 - 1.8倍,胞质Ca2+浓度比正常水平高2 - 4倍。从30天到350天,用曲美他嗪(抗缺血药物)进行长期口服治疗(每天18 mg/kg)比标准的Ca2+阻滞剂维拉帕米更有效。曲美他嗪使CMH的中位生存时间增加了57%,肥大消失。CMH中的总Ca2+水平恢复到正常叙利亚仓鼠(F1B)的水平。胞质Ca2+过载被限制在约2倍的因子范围内。因此,曲美他嗪具有抗Ca2+特性,可有效提高CMH的生存率并减轻心脏和肝脏肥大。这表明曲美他嗪在预防类似病因的充血性心力衰竭方面可能具有价值。

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