Liu Li, Zhang Xiaojin, Qian Bo, Min Xiaoyan, Gao Xiang, Li Chuanfu, Cheng Yunlin, Huang Jun
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Eur J Heart Fail. 2007 Aug;9(8):762-9. doi: 10.1016/j.ejheart.2007.03.007. Epub 2007 May 4.
Oxidative stress and myocyte apoptosis are thought to play an important role in the pathogenesis, progression and prognosis of heart failure (HF). Heat shock protein 27 (Hsp27) has been found to confer resistance to oxidative stress in cultured cells; however, the role of Hsp27 in in-vivo hearts remains to be determined.
To investigate the effects of Hsp27 over-expression on doxorubicin-induced HF.
Transgenic mice (TG) with cardiac specific over-expression of Hsp27 and their wild type littermates (WT) were challenged with doxorubicin (25 mg/kg, IP) to induce HF. At day 5, TG mice had significantly improved cardiac function and viability and decreased loss of heart weight following doxorubicin exposure compared with WT. In another parallel experiment, doxorubicin-induced increased levels of reactive oxygen species, protein carbonylation, apoptosis and morphologic changes were detected in the mitochondria in WT hearts, whereas these effects were markedly attenuated in TG hearts. In addition, upregulation of heat shock protein 70 and heme oxygenase-1 was present in the TG hearts after doxorubicin stimulation in comparison to WT hearts.
These findings indicate that Hsp27 may play a key role in resistance to doxorubicin-induced cardiac dysfunction.
氧化应激和心肌细胞凋亡被认为在心力衰竭（HF）的发病机制、进展和预后中起重要作用。已发现热休克蛋白27（Hsp27）可使培养细胞对氧化应激产生抗性；然而，Hsp27在体内心脏中的作用仍有待确定。
研究Hsp27过表达对阿霉素诱导的心力衰竭的影响。
用阿霉素（25mg/kg，腹腔注射）诱导心脏特异性过表达Hsp27的转基因小鼠（TG）及其野生型同窝小鼠（WT）发生心力衰竭。在第5天，与WT相比，TG小鼠在阿霉素暴露后心脏功能和活力显著改善，心脏重量损失减少。在另一平行实验中，在WT心脏的线粒体中检测到阿霉素诱导的活性氧水平升高、蛋白质羰基化、细胞凋亡和形态学变化，而在TG心脏中这些作用明显减弱。此外，与WT心脏相比，阿霉素刺激后TG心脏中热休克蛋白70和血红素加氧酶-1上调。
这些发现表明，Hsp27可能在抵抗阿霉素诱导的心脏功能障碍中起关键作用。
