基于IGF-1研究黑地黄丸调控5/6肾切除大鼠BMSCs归巢及RTECs凋亡的作用

胰岛素样生长因子-1（IGF-1）是骨髓间充质干细胞（BMSCs）分泌的细胞因子之一，不仅可以促进BMSCs归巢至残肾，而且具有抗肾小管上皮细胞（RTECs）凋亡的作用，而RTECs凋亡是肾间质纤维化（RIF）的始动因素。本课题组前期研究显示，黑地黄丸可以抑制RIF，减轻肾小球硬化，体外实验亦证实该药能够促进肾衰大鼠BMSCs增殖及分泌IGF-1。本研究拟通过体内实验观察黑地黄丸通过影响BMSCs分泌IGF-1干预BMSCs在肾小管中的分布、BMSC归巢、RTECs凋亡信号的表达；体外实验通过粘附实验、迁移实验和RTECs凋亡研究观察黑地黄丸的干预作用，验证黑地黄丸促进BMSCs自分泌IGF-1提高BMSCs至残肾的归巢率、通过旁分泌IGF-1抑制RTECs凋亡、延缓RIF的假说，进一步探索黑地黄丸肾保护作用的机理，为中医药治疗慢性肾衰寻找新靶点。

Insulin-like growth factor -1 (IGF-1) is one of the cytokines secreted from bone marrow mesenchymal stem cells (BMSCs), not only can promote the BMSCs homing to the remnant kidney, but also has antagonistic effect on renal tubular epithelial cells (RTECs) apoptosis. It is known that RTECs apoptosis is the initial factor of renal interstitial fibrosis (RIF). Our previous research shows that the Hei Di-huang Bolus can inhibit RIF, reduce glomerular sclerosis, and vitro experiment indicated that the drug can promote BMSCs proliferation and secreting IGF-1. This study intends to verify the hypothesis that Hei Di-huang Bolus can promote BMSCs autocrine IGF-1 to improve the homing rate of itself to remnant kidney and can paracrine IGF-1 to inhibit RTECs apoptosis and delay RIF through both vivo and vitro experiments. The vivo experiment intends to observe the effect of Hei Di-huang Bolus on BMSCs distribution in renal tubules, homing of BMSCs and and expression of the RTECs apoptosis signals. The vitro experiment intends to observe the effect of Hei Di-huang Bolus on adhesion and migration of BMSCs and RTECs apoptosis. This research intends to further explore the mechanism of the protective effect of Hei Di-huang Bolus on kidney and find a new target for the treatment of CRF with traditional Chinese medicine.