Abstract: Objective　To investigate the effect and mechanism of substance P (SP) on the proliferation, migration and vessel endothelial cell differentiation of human bone marrow mesenchymal stem cells (BMSCs) in high glucose environment, and to lay a foundation for the treatment of diabetic complications such as skin ulcers. Methods　The cell high glucose model was divided into the high glucose control group, the high glucose SP group and the high glucose Akt inhibitor group. And BMSCs cultured in normal environment were used as the normal control group. CCK-8 assay was used to detect the cell proliferation. Transwell cell migration assay was used to determine the cell migration number of BMSCs. In each group, the differentiation of vascular cells was induced, and ELISA was used to detect CD31 protein content of BMSCs after differentiation for each group. Matrix mesh formation test was used to detect the angiogenesis ability. Western blot assay was used to detect the expression levels of Akt and phosphorylated Akt (p-Akt) in each group of BMSCs. Results　Compared with the control group and high glucose control group, the absorbance (A450) value, migration number, CD31 protein content, mesh number, relative expression levels of Akt and P-Akt protein were decreased in the high glucose SP group. Compared with the high-glucose group, the A450 value, migration number, CD31 protein content, mesh number, relative expression levels of Akt and P-Akt protein were significantly increased in the high-glucose SP group (P＜0.01). Compared with the high-glucose SP group, these indexes were all reduced in the high glucose Akt inhibitor group (P＜0.01). Conclusion　In high glucose environment, SP promotes the proliferation, migration and angiogenic differentiation of BMSCs by activating Akt pathway.

Key words: substance P, mesenchymal stromal cells, cell proliferation, cell movement, high glucose cell model, differentiation of angioblasts