斑块内新生微血管是动脉粥样硬化（AS）进展及不稳定斑块形成的关键因素，抑制斑块内微血管新生是目前亟待解决的科学问题。①我们前期发现丹参单体隐丹参酮能显著抑制体外血管新生，②文献报道隐丹参酮能与蛋白酪氨酸磷酸酶SHP-2结合抑制其活性，③我们发现ShRNA沉默SHP-2表达后内皮细胞血管新生明显减少，④我们在可诱导内皮敲除SHP-2的小鼠模型（SHP-2IECKO）中发现SHP-2诱导敲除后视网膜中新生血管末端数量显著减少，提示隐丹参酮可能通过抑制SHP-2进而抑制血管新生。为此，我们拟采用ApoE-/-和SHP-2IECKO/ApoE-/-小鼠建立AS模型，前者给予隐丹参酮干预，分析药物抑制和基因缺失分别对AS进展及斑块内微血管新生的影响；在体外运用SHP-2过表达、抑制和基因沉默等方法，进一步明确隐丹参酮及其靶点SHP-2在内皮细胞血管新生中的作用，为其对AS的防治提供新的理论依据。

Atherosclerotic plaque neovascularization is one of the key factors for the development of atherosclerosis (AS) and the formation of unstable plaques. Inhibition of plaque neovascularization is a scientific problem to be solved urgently at present. ①In our previous study, we found that cryptotanshinone significantly inhibit angiogenesis in vitro. ②It is reported that cryptotanshinone could inhibit the activity of the protein tyrosine phosphatase SHP-2 by combination with its PTP domain. ③We found that silencing expression of SHP-2 by shRNA significantly decreased angiogenesis in vitro. ④Moreover, in the endothelial-specific inducible SHP2 knockout mice, we found that SHP-2 knockout decrease neovascularization in the retina. These results suggest that cryptotanshinone might inhibit angiogenesis through SHP-2. Therefore, we will investigate the effect of cryptotanshinone in ApoE-/- AS model or ApoE-/-mice induced with endothelial-specific knockout of SHP-2 on the progress of AS and plaque neovascularization. In vitro, we will promote SHP-2 expression and inhibit or silence SHP-2 expression to further clarify the effects of cryptotanshinone on angiogenesis and signal pathway. The results will provide a theoretical basis for the prevention and treatment of AS.