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不同剂量维 A 酸对心脏重构的影响。

Influence of different doses of retinoic acid on cardiac remodeling.

机构信息

Internal Medicine Department, Botucatu Medical School, São Paulo State University, Botucatu, Brazil.

出版信息

Nutrition. 2011 Jul-Aug;27(7-8):824-8. doi: 10.1016/j.nut.2010.08.011. Epub 2010 Oct 29.

DOI:10.1016/j.nut.2010.08.011
PMID:21035307
Abstract

OBJECTIVE

The role of retinoic acid in promoting postnatal heart alterations is still unclear. The aim of this study was to evaluate whether the cardiac alterations caused by all-trans- retinoic acid (ATRA) in normal adult rat hearts are physiologic or pathologic and if these alterations are dose-dependent.

METHODS

Rats were allocated into a control group that received a diet without ATRA (n=16), a group that received 0.3 mg of ATRA/kg of diet (n=17), a group that received a diet containing 10 mg of ATRA/kg (n=18), or a group that received 50 mg of ATRA/kg in the diet (n=18). After 4 wk, the animals were evaluated echocardiographically, morphologically, and biochemically.

RESULTS

The 50-mg ATRA group presented cardiac hypertrophy with maintenance of cardiac geometry and increased systolic function, whereas diastolic function was similar to that of the control group. In addition, progressive increases in the ATRA dose resulted in gradual augmentations of left atrial diameter, left ventricular diastolic and systolic diameters, left ventricular mass index, cardiac output, cardiac index, and aortic velocity. The ATRA did not produce alterations in interferon-γ and tumor necrosis factor-α cardiac levels, interstitial collagen volume fraction, or the intensity and localization of connexin-43. In addition, no alteration was observed in β-hydroxyacyl coenzyme A dehydrogenase, lactate dehydrogenase, or citrate synthase, suggesting that cardiac energetic metabolism was preserved with ATRA.

CONCLUSION

These results suggest that ATRA produced dose-dependent effects and cardiac remodeling that is more compatible with a physiologic response.

摘要

目的

视黄酸在促进出生后心脏改变中的作用尚不清楚。本研究旨在评估全反式视黄酸(ATRA)在正常成年大鼠心脏中引起的心脏改变是生理性的还是病理性的,以及这些改变是否具有剂量依赖性。

方法

将大鼠分为对照组(n=16),即给予不含 ATRA 的饮食;0.3mg/kg 饮食 ATRA 组(n=17);10mg/kg 饮食 ATRA 组(n=18);50mg/kg 饮食 ATRA 组(n=18)。4 周后,对动物进行超声心动图、形态学和生化评估。

结果

50mg ATRA 组出现心肌肥厚,保持心脏几何形状,收缩功能增强,而舒张功能与对照组相似。此外,随着 ATRA 剂量的逐渐增加,左心房直径、左心室舒张和收缩直径、左心室质量指数、心输出量、心指数和主动脉速度逐渐增加。ATRA 未引起干扰素-γ和肿瘤坏死因子-α心脏水平、间质胶原容积分数或连接蛋白 43 的强度和定位的改变。此外,β-羟酰基辅酶 A 脱氢酶、乳酸脱氢酶或柠檬酸合酶未见改变,提示 ATRA 保留了心脏能量代谢。

结论

这些结果表明,ATRA 产生了剂量依赖性的作用和心脏重塑,与生理性反应更相容。

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