延长供心冷保存时间，提高保存质量，减轻心肌缺血再灌注损伤是目前心脏移植领域迫切需要解决的临床问题。本课题观察TLR4基因突变小鼠在供心冷保存和移植后再灌注两个阶段，心肌细胞凋亡、炎症反应和氧化应激等方面的变化，探讨TLR4在冷保存心脏移植中的作用。建立小鼠离体心脏Langendorff 灌注模型和异位心脏移植模型，通过含有TLR4 siRNA的冷保存液灌注并保存供心，转染心肌后抑制TLR4基因表达，明确 TLR4 siRNA 冠脉灌注法对供体心脏基因转染的效率，从心脏功能和心肌损伤角度探讨其对供心冷缺血性和再灌注损伤的保护作用。为今后临床心脏移植心肌保护的发展提供一种新的方法和理论依据。

Despite major achievements in heart transplantation, we still face some urgent problems such as: prolonging the preservation period of donor heart,.improving myocardial function and metabolism, and reducing myocardial ischemia/ reperfusion injury. To compare the role of Toll-like receptor-4(TLR4)in heart transplantation using cold preservation solution,two types of mice were used in this study:free wild type mice(C3H/HeN)and TLR-4 gene mutation type(C3H/HeJ)on the two periods of static cold storage and reperfusion after transplantation.The changes of myocardial apoptosis, inflammatory responses and oxidative stress and so on are observed. We establish the model of isolated heart Langendorff perfusion and the model of heterotopic heart transplantation. We develope the preservation solution consisting of siRNA that targets TLR4,and perfuse donor hearts with the siRNA solution and silence TLR4 gene in the preservation period. The effectiveness of siRNA uptake by heart tissues is determined. We can discuss the protection on the donor heart cold ischemic and reperfusion injury from cardiac function and myocardial injuries. This study will demonstrate a new hypothesize and method for donor heart protection, and can potentially have significance in clinical application.