出血造成的JNK3激活是脑出血患者神经元损伤的重要原因。研究表明：Wnt信号通路介导蛋白Dvl-1的DEP结构域可通过活化MKK4/7功能，进而激活JNK3；相反，DEP结构域变异，则能阻断这一过程；而β-arrestin2作为支架蛋白分别与Dvl1和JNK3结合，构成激活JNK3的特异信号模块。.我们的前期研究发现：脑出血后局部神经组织Wnt5a表达明显升高，同时β-arrestin2参与的Dvl1-MKK4-JNK3信号模块表达增加，提示Wnt5a可能通过这一信号通路直接参与出血后的JNK3激活。据此，我们提出脑出血后神经元损伤的新通路，即：Wnt5a通过刺激β-arrestin2募集并组装Dvl1-MKK4-JNK3信号模块，进而激活JNK3。本课题拟用免疫印迹、免疫共沉淀、免疫荧光等技术，从整体、细胞、分子水平进一步验证上述假设，为治疗脑出血神经损伤提供新的思路和靶点。

Activation of JNK3 is one of the main causes of neuronal damage in patients with intracerebral hemorrhage. In the Wnt signal pathway, the DEP domain in Dvl1 can activate MKK4/7 and further activate JNK3. However, if the DEP domain is altered, it would fail to activate JNK3. β-arrestin2 has been reported as a scaffold which binds Dvl1 and JNK3. .We have found a significant increase in the expression of Wnt5a and the Dvl1-MKK4-JNK3 signal module in the traumatized brain tissue following intracerebral hemorrhage. These data suggested that Wnt5a may activate the signal module and then further activate JNK3 indrectly. Based on the above data, we propose a new signal pathway: Wnt5a→Dvl1-MKK4-JNK3 signal module→activation of JNK3. Using immunobloting, immunoprecipitation, Western blotting and laser scanning confocalmicroscope, we intend to clarify this assumption. This study may offer new ideas and new targets for effective treatment of intracerebral hemorrhage.