胸腺素β4 (Tβ4)因其促血管新生作用,成为治疗缺血性心脏病的有效候选药物，但其促血管新生的具体分子机制远未阐明。前期我们通过转录物组测序，首次发现Tβ4作用于微血管内皮细胞后显著上调长链非编码RNA-MALAT1，并证明MALAT1是Tβ4促血管生成的重要分子。那么Tβ4如何上调MALAT1？MALAT1又如何促进血管新生？是本课题的关键科学问题。通过序列分析和文献复习，我们提出“Tβ4通过ILK/AKT/GSK-3β途径抑制转录因子c-Myc泛素化降解,进而上调MALAT1;MALAT1又通过竞争性抑制miR503的功能，发挥促血管生成作用”假说。本课题将通过多种分子生物学手段，探讨Tβ4/MALAT1/miR503促进血管新生的分子机制并证实上述假说。本课题首次证明长链非编码RNA在Tβ4作用机制中的重要作用，将为Tβ4的广泛应用奠定理论基础，也为治疗性血管新生提供新思路和新靶点。

Thymosin beta 4 (Tβ4) is a pleiotropic peptide and participates in promotion angiogenesis, which is expected to become a fundamental tool for the treatment of ischemic heart disease and attracted many attentions, but its Molecular mechanism is far to confirm. Though the RNA sequence earlier, for the first time, we found the function of Tβ4 on the microvascular endothelial cells to promote Long chain non-coding RNA-MALAT1, which proved MALAT1 is a vital molecule for angiogenesis promotion. So, how Tβ4 regulates MALAT1? And what is the molecular mechanism of the MALAT1 to promote angiogenesis? Both are the typical problems to be solved in this research. Through preview researches and analysis of RNA sequences, these questions will be to verify with the following hypothesis: Tβ4 inhibits the ubiquitin degradation of the transcription factor c - Myc by ILK/AKT/GSK - 3 beta which results in raising the MALAT1 expression. Ultimately, MALAT1 promotes angiogenesis and proliferation of vascular endothelial cells, through a competitive combination with miR-503. Numbers of molecular biological techniques will be used to prove the molecular mechanism that Tβ4/MALAT1/miR503 promotes angiogenesis in this study. This study will demonstrate the importance of Long chain non-coding RNA in the mechanism of Tβ4 for the first time, which provide foundations for widespread use of Tβ4, and new ways or target for the angiogenesis promotion.