研究表明，糖尿病勃起功能障碍（ED）药物治疗效果不理想与海绵体内皮功能障碍、平滑肌收缩性增强及细胞过度凋亡等多因素相关。在心血管系统中，2型非受体型酪氨酸激酶（JAK2）活化可导致活性氧（ROS）大量生成、平滑肌收缩性增强以及血管内皮和平滑肌细胞过度凋亡。申请者利用JAK2的化学抑制剂AG490进行的预实验发现，抑制JAK2活化后，可通过减少活性氧生成、降低海绵体平滑肌收缩性、减少海绵体内皮和平滑肌细胞凋亡，进而显著改善糖尿病ED大鼠勃起功能。为进一步研究JAK2作为ED治疗新靶点的可行性，本项目拟利用内皮细胞JAK2条件性敲除小鼠、平滑肌细胞JAK2条件性敲除小鼠和全身JAK2条件性敲除小鼠三种模型，在体外、体内和分子水平深入研究JAK2对高糖环境下阴茎海绵体内皮细胞和平滑肌细胞功能及数量的影响，从而阐明JAK2对勃起功能的影响和作用机制，为开发糖尿病ED特异性靶向治疗新药提供理论基础。

A large number of research results show that the effectiveness of drug treatment on diabetic erectile dysfunction (ED) is poor, the main mechanisms of which are associated with endothelial dysfunction, and increased smooth muscle tone along with excessive apoptosis of penile tissues. In the cardiovascular system, it has been reported that janus kinase 2 (JAK2) activition lead to excessive production of reactive oxygen species (ROS), increased vascular tone and excessive apoptosis of vascular endothelial and smooth muscle cells. In our preliminary experiments, we found that the JAK2 chemical inhibitor AG490 treatment was able to restore erectile dysfunction in diabetic rats. The main mechanisms of this improvement were suggested with decreased reactive oxygen species level, reduced cavernous smooth muscle tone and increased contents of endothelium and smooth muscle in penile tissue. For further study, we design this research to explore the role of JAK2 on ED and underlying mechanisms in Vitro and in Vivo using inducible endothelial cells specific JAK2 knockout mouse model, inducible smooth muscle cells specific JAK2 knockout mouse model and inducible JAK2 knockout mouse model. Finally, this work will have the potential to characterize a new molecular target and theoretical basis for treating diabetic ED.