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人类阿波利波蛋白AI基因转移减少了实验性糖尿病心肌病的发展
Sophie Van Linthout1, Frank Spillmann, Alexander Riad
1Abteilung für Kardiologie und Pneumologie, Charité-Universitätsklinikum Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Circulation
|March 12, 2008
概括
阿波利波蛋白A-I (apoA-I) 的基因转移增加了高密度脂蛋白 (HDL) 水平,有效地减少了大鼠的糖尿病心肌病. 这种疗法减轻了心脏氧化应激,炎症和亡,改善了心脏功能.
科学领域:
- 心血管生物学 心血管生物学
- 代谢疾病 代谢疾病
- 基因治疗 基因治疗
背景情况:
- 糖尿病心肌病症的特点是心脏氧化应激,炎症,纤维化和亡.
- 高密度脂蛋白 (HDL) 具有抗氧化,抗炎和抗性质.
研究的目的:
- 评估通过人类阿波利波蛋白A-I (apoA-I) 的基因转移 (GT) 来增加HDL是否可以预防糖尿病心肌病.
主要方法:
- 鼠接受了链毒素 (STZ) 诱导糖尿病,然后静脉注射GT的apoA-I表达载体 (Ad.hapoA-I) 或对照载体 (Ad.Null).
- 心脏功能,氧化应激,炎症,纤维化,亡以及相关的分子途径在GT后6周被评估.
主要成果:
- ApoA-I GT显著增加了HDL胆固醇水平,并在体内改善了左心室收缩性和体外心肌细胞收缩性.
- 心脏氧化应激,心肌内炎症,纤维化和糖原积累在apoA-I GT组中减少.
- 亡标志物 (亡酶活性) 减少,而抗亡标志物 (Bcl-2/Bax比) 增加,导致心肌细胞和内皮细胞亡减少.
结论:
- ApoA-I的基因转移有效地减少了STZ诱导的糖尿病心肌病的发展.
- 保护作用与改善心脏功能和减少疾病的病理特征有关.
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