阴虚动物血清经PPARγ信号通路调控巨噬细胞极化及其抗肿瘤功能的机制研究

Traditional Chinese medicine proposes that Yin deficiency may be play critical roles in progression of cancer，while Western medicine thinks that tumor microenvironment (TME) performs a pivotal function in the process of cancer development and metastasis. So will Yin deficiency have an impact on the TME? Macrophage(MΦ)—an important cell in TME-- has two kinds of polarized phenotype: M1 MΦ can play an anti-tumor effect, while M2 MΦ can promote tumor growth and metastasis. By preliminary experiments we found that the serum of animals with Yin deficiency can inhibit the M1 MΦ polarization and reduce their ability of killing hepatocarcinoma cells. Therefore, it is suggested that yin deficiency may influence the occurrence and development of tumor by regulating macrophage polarization and function. In order to further explore the mechanisms of which substances in Yin deficiency serum affecting the macrophage polarization, this research intends to detect the differences of serum fatty acid metabolism by gas chromatography and the changes of PPAR gamma and NF- kappa B which are the relevant signaling pathways to macrophage polarization. This study will verify and enrich the hypothesis that Yin deficiency is assosiated with cancer from the perspective of the tumor microenvironment and lay the foundation for the further research which using the “ Nourishing Yin ” means recover the anti-tumor function of macrophage.

中医“阴虚癌瘤相关假说”提出阴虚可能是肿瘤发病的主要起因之一，而西医则认为肿瘤微环境在肿瘤的发展和转移中起着重要作用，那么阴虚是否会对肿瘤微环境产生影响呢？巨噬细胞是肿瘤微环境中的一类重要细胞，其有两种极化功能表型：M1型发挥抗肿瘤作用，M2型则促进肿瘤的生长和转移。通过前期实验我们发现阴虚动物血清能抑制巨噬细胞的M1型极化并降低其对肝癌细胞的杀伤能力，从而提示阴虚可能通过调控巨噬细胞的极化和功能来影响肿瘤的发生发展。为进一步探讨是阴虚血清中的何种物质通过何种机制影响了巨噬细胞的极化，本课题拟通过气相色谱技术研究阴虚动物血清中脂肪酸代谢谱的改变，同时检测巨噬细胞极化相关信号通路PPARγ和NF-κB的活性变化。本课题旨在从肿瘤微环境的角度验证并丰富“阴虚癌瘤相关假说”，为利用中医“滋阴”的方法恢复巨噬细胞的抗肿瘤功能奠定基础。