过继转输未成熟树突状细胞对心肌梗死后左室重构的影响

A recent meta-analysis assessing the results of stem cell therapy for patients with acute myocardial infarction (MI) demonstrated no net beneficial effects on outcomes, except for a small improvement in ejection fraction. The underlying mechanism of stem cell therapy is speculated to be secondary to expression and secretion of paracrine factors rather than direct differentiation of the injected progenitor cells to cardiac myocytes. Thus, we put forward the hypothesis that adoptive transfer of a specialized immune cell after MI may have better outcomes than stem cell therapy. Immature dendritic cell (imDC) has the ability to inhibit T cell activation, and to induce and promote regulatory T cell development and expansion. Our previous studys found that atorvastatin inhibits the immune maturity of dendritic cells induced by angiotensin-2 via PI3K/Akt/Nrf 2 pathway. Our preliminary experiments demonstrated that atorvastatin inhibits the immune maturity of DC induced by necrotic cardiomyocyte supernate (NCS). The goal of this study is to investigate whether adoptive transfer of imDC induced by atorvastatin and NCS could suppress the inflammation after MI and improve left ventricular remodeling.

干细胞治疗对于急性心肌梗死（MI）患者终点事件并无有益作用，仅轻度的改善左室射血分数。研究显示干细胞移植获益的主要机制为旁分泌作用，即通过分泌细胞因子，以抑制MI后的炎症反应。我们设想在MI后过继转输专职免疫细胞，以期能更好的抑制MI后炎症反应。未成熟树突状细胞（immature dendritic cell，imDC）具有负向免疫调节功能，其能抑制T细胞激活，诱导调节性T细胞形成，进而抑制T细胞免疫炎症。我们前期研究发现阿托伐他汀通过PI3K/AKT信号通路介导Nrf 2的核转位，可抑制angiotensin-2所诱导的DC免疫成熟。在预实验中我们发现心肌细胞坏死悬液（necrotic cardiomyocyte supernate, NCS）可诱导DC成熟，而阿托伐他汀可抑制DC成熟。因此，本项目拟探讨过继转输阿托伐他汀+NCS预处理的imDC对MI后炎症反应、左室重构的影响。