巴西苏木素上调Gr-1+CD11b+髓样细胞的Hoxa3促进糖尿病下肢血管新生的实验研究

We recently found Gr-1+CD11b+ myeloid cells can promote angiogenesis and improve wound healing in diabetic mice, however,the Gr-1+CD11b+ myeloid cells from diabetic mice failed to stimulate neovascularization and have aberrant proliferative,chemotaxis,adhesion and differentiation potential. Overexpression of transcriptional factor Hoxa3 in Gr-1+CD11b+ myeloid cells promotes angiogenesis in diabetic mice by reversing diabetic phenotype of Gr-1+CD11b+ myeloid cells. Our prelimilary experiments showed brazilin upregulated the Hoxa3 in diabetic Gr-1+CD11b+ myeloid cells, thus,we hypothesized the brazilin could be used to treat the diabetic peripheral arterial obstructive disease by reversing the diabetic phenotype of Gr-1+CD11b+ myeloid cells. By cell culture, animal experiment,immunostaining,qPCR,western blot, cell sorting and gene chip et al, we determine that the brazilin promote angiogenesis in diabetic mice by upregulating the Hoxa3 and reversing the diabetic phenotype of Gr-1+CD11b+ myeloid cells，and futher eluicidate the mechanism of promoting angiogenesis of ischemic limb. This will provide new target for the treatment of diabetic ischemic limb by brazilin.

我们近期研究发现Gr-1+CD11b+髓样细胞可促进糖尿病下肢的血管新生和伤口愈合,但是糖尿病源性的Gr-1+CD11b+髓样细胞并不能刺激血管新生，并且在增殖、趋化、粘附及分化潜能方面存在异常。糖尿病源性的Gr-1+CD11b+髓样细胞过表达转录因子Hoxa3能逆转其糖尿病表型，增强血管新生。我们的预实验证明苏木的活性成分巴西苏木素可上调糖尿病源性Gr-1+CD11b+髓样细胞的Hoxa3。因此提出假说：巴西苏木素可通过逆转糖尿病源性的Gr-1+CD11b+髓样细胞的表型治疗糖尿病引起的血管闭塞性硬化。本研究通过细胞培养、动物实验、免疫染色、定量PCR、蛋白印迹、细胞分选、基因芯片等方法，明确巴西苏木素上调Hoxa3，逆转糖尿病源性的Gr-1+CD11b+髓样细胞表型，增强缺血下肢的血管新生, 并进一步阐明其作用机制，为巴西苏木素治疗糖尿病缺血性下肢病变提供新靶点。