目的探讨BMP和Notch信号通路介导红景天苷诱导骨髓间充质干细胞(MSCs)向神经细胞定向分化的分子机制。方法实验分为对照组、红景天苷诱导组和阻断组。利用细胞免疫荧光化学方法、Real-Time PCR方法和Western blotting方法分别研究了红景天苷对MSCs的增殖、形态以及对BMP和Notch信号通路的影响。结果红景天苷影响MSCs的增殖且促进其形成神经元样细胞;细胞免疫荧光结果显示,红景天苷可降低Notch1和Jadge1阳性表达率(P<0.05);红景天苷诱导细胞12~72 h时,Notch1和Hes1 m RNA表达丰度明显下调(P<0.05);特异性阻断剂DAPT阻断Notch信号通路后,神经元细胞标志分子NSE、MAP-2和β-tubulin III m RNA和NSE、β-tubulin III蛋白的表达水平与阻断前比较显著上调(P<0.05)。12 h时Smad5和Smad8 m RNA的表达水平显著上调(P<0.01),且12和24 h时Smad1/5/8蛋白表达上调(P<0.05);Noggin阻断BMP信号通路后,NSE、MAP-2和β-tubulin III m RNA的表达丰度与诱导组比较明显下调(P<0.05);DAPT和Noggin同时阻断Notch和BMP信号通路后,与单独阻断BMP信号通路后比较,MAP-2和β-tubulin III m RNA的表达上调,NSE和β-tubulin III蛋白的表达水平上调(P<0.05)。结论红景天苷通过抑制Notch信号通路、激活BMP信号通路诱导MSCs向神经元细胞定向分化。 Objective To investigate the molecular mechanism of salidroside-induced directional differentiation of bone marrow mesenchymal stem cells (MSCs) into neurons by BMP and Notch signaling pathway. Methods The experiment was divided into control group, salidroside induction group and blocking group. Real-time PCR and Western blotting were used to study the effects of salidroside on proliferation and morphology of MSCs and their effects on BMP and Notch signaling pathways respectively. Results Salidroside affected the proliferation of MSCs and promoted the formation of neuron-like cells. The results of immunofluorescence showed that salidroside could reduce the expression of Notch1 and Jadge1 (P <0.05) At 72 h, the expression abundance of Notch1 and Hes1 m RNA was significantly down-regulated (P <0.05). After blockade of Notch signaling pathway by specific blocker DAPT, NSE, MAP-2 and β-tubulin III m RNA And NSE, β-tubulin III protein levels were significantly up-regulated compared with that before the blocking (P <0.05). The expression of Smad5 and Smad8 mRNA increased significantly at 12 h (P <0.01), and at 12 and 24 h (P <0.05). After Noggin blocked the BMP signaling pathway, NSE, MAP 2 and β-tubulin III m RNA were significantly down-regulated compared with the induction group (P <0.05). After DAPT and Noggin blocked both Notch and BMP signaling pathway, compared with blocking BMP signaling pathway alone, MAP- 2 and β-tubulin III m RNA were up-regulated, and the expressions of NSE and β-tubulin III were up-regulated (P <0.05). Conclusion Salidroside can induce MSCs to differentiate into neuronal cells by inhibiting Notch signaling pathway and activating BMP signaling pathway.