心力衰竭（心衰）是心血管疾病的主要死亡原因。心肌干细胞（CSC）是一种能定向分化为心肌细胞的干细胞类型，被认为是最有希望以完全心肌再生方式用于心肌替代治疗的干细胞类型。如何动员CSC并促进其分化为心肌细胞是心衰领域的研究热点和希望。经典WNT/β-连环蛋白信号通路是调控CSC自我更新与分化的重要通路，过氧化物酶增殖体活化受体-γ（PPAR-γ）激动剂可直接抑制该通路的转导。我们发现，心肌PPAR-γ过表达可致心脏扩大及心衰，而心梗后心衰大鼠心肌PPAR-γ表达上调，CSC数量明显减少，且PPAR-γ激动剂可使CSC进一步减少，但对正常心脏CSC不产生影响。为此我们提出PPAR-γ激活通过WNT/β-连环蛋白通路负向调控小鼠CSC增殖及分化的假设，利用梗死后心衰鼠模型和Tet-on/off表达调控系统等进行论证，探讨PPAR-γ对CSC心肌再生的影响及机制，为CSC治疗心衰奠定一定理论基础。

Heart failure (HF) is the main death cause of cardiovascular diseases. Cardiac stem cells (CSCs), a knid of stem cell with the ability of directional differentiation into myocytes, is deemed to be the most hopeful stem cell adopted as the myocardial replacement therapy with the manner of complete myocytes regeneration. How to mobilize CSCs and promote CSCs' differentiation into myocytes is the hot point and hope in HF study field. Canonical WNT/β-catenins pathway is the pivotal pathway to regulate the renew and differentiation of CSCs, and peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist can directly inhibit the transduction of WNT/β-catenins pathway. Our study found that myocardial overexpression of PPAR-γ could directly induce enlarged heart and heart failure.In addition, myocardial PPAR-γ expression would significantly increase in rats with heart failure after myocardial infarction, and CSC number would greatly decrease.After the treatment of PPAR-γ agonist, CSC number could further decrease, but it had no significant effect on CSC in normal heart. Accordingly, we hypothesize that activating PPAR-γ can negatively regulate the generation and differentiation of CSC by WNT/β-catenins pathway. The present study will evaluate the effects of PPAR-γ on myocardial generation and renew and discuss the related mechanisms, which will help to provide the theory base for the future treatment of heart failure by CSC.