激活Sonic hedgehog通路改善1型糖尿病小鼠内皮祖细胞功能

Activating Sonic hedgehog pathway can improve the impaired function of endothelial progenitor cells in type 1 diabetic mice

目的研究激活Sonic hedgehog通路对1型糖尿病小鼠内皮祖细胞(EPCs)生物学功能的影响。方法用链脲佐菌素(STZ)诱导建立1型糖尿病小鼠模型;采用密度梯度离心法分离并培养糖尿病小鼠骨髓EPCs;体外给予Sonic hedgehog(Shh)信号通路配体蛋白Shh和受体激动剂SAG,通过MTT法、改良Boyden小室、Matrigel和β-半乳糖苷酶分别检测各组EPCs的增殖、迁移、小管形成和衰老的功能性指标。结果 1型糖尿病小鼠EPCs与正常对照组相比功能明显下降,体外给予Shh蛋白和受体激动剂SAG,可促进糖尿病EPCs增殖,减少衰老,改善迁移和小管形成能力。结论体外激活Sonic hedgehog通路可以改善1型糖尿病小鼠内皮祖细胞受损的功能。

Aim To study the effect of activating Sonic hedgehog （Shh） pathway on the function of endothelial progenitor cells （EPCs） in type 1 diabetic mice. Methods EPCs were isolated and cultured by density gradient method from diabetic mice. The effects of ShhN-terminal peptide and agonist SAG on EPCs prolifera- tion were evaluated by using the MTr colorimetric as- say. EPCs migration was measured by Transwell meth- od. EPCs tube formation ability was estimated by Matrigel. EPCs senescence activity was determined by β-galactosidase staining. Results Compared with control mice, the function of EPCs in type 1 diabetic mice was impaired. The proliferation, migration and tube formation of diabetic EPCs could be promoted by Shh peptide and agonist SAG. The senescence of dia- betic EPCs could be decreased by Shh peptide and ag-onist SAG. Conclusion Activating Shh signaling pathway can improve the impared function of diabetic EPCs in type 1 diabetic mice.