Department of Bioengineering, Hanyang University , Seoul , Republic of Korea .
J Drug Target. 2013 Nov;21(9):822-9. doi: 10.3109/1061186X.2013.829072. Epub 2013 Aug 19.
Heat shock proteins, acting as molecular chaperones, protect heart muscle from ischemic injury and offer a potential approach to therapy. Here we describe preparation of an injectable form of heat shock protein 27, fused with a protein transduction domain (TAT-HSP27) and contained in a hybrid system of poly(d,l-lactic-co-glycolic acid) microsphere and alginate hydrogel. By varying the porous structure of the microspheres, the release of TAT-HSP27 from the hybrid system was sustained for two weeks in vitro. The hybrid system containing TAT-HSP27 was intramyocardially injected into a murine myocardial infarction model, and its therapeutic effect was evaluated in vivo. The sustained delivery of TAT-HSP27 substantially suppressed apoptosis in the infarcted site, and improved the ejection fraction, end-systolic volume and maximum pressure development in the heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27 using a hybrid system may present a promising approach to the treatment of ischemic diseases.
热休克蛋白作为分子伴侣，可保护心肌免受缺血性损伤，为治疗提供了一种潜在的方法。在这里，我们描述了一种可注射形式的热休克蛋白 27 的制备方法，该蛋白与蛋白转导结构域（TAT-HSP27）融合，并包含在聚（D，L-乳酸-共-乙醇酸）微球和藻酸盐水凝胶的混合系统中。通过改变微球的多孔结构，TAT-HSP27 从混合系统中的释放可以在体外持续两周。将含有 TAT-HSP27 的混合系统注入到小鼠心肌梗死模型的心肌内，并在体内评估其治疗效果。TAT-HSP27 的持续递送显著抑制了梗死部位的细胞凋亡，并改善了心脏的射血分数、收缩末期容积和最大压力发展。使用混合系统局部和持续递送抗细胞凋亡蛋白（如 HSP27）可能为治疗缺血性疾病提供一种有前途的方法。
