腺苷转运体介导腺苷信号通路的分子机制——阴茎康复的新靶点

目前临床上采用的阴茎康复方法，无论从疗效还是依从性均面临难以克服的障碍, 急需从全新的视角来解决。 我们及他人的前期结果表明提升阴茎海绵体上腺苷浓度可致阴茎平滑肌松弛，过量可致阴茎异常勃起。腺苷转运体是决定细胞内外腺苷浓度的关键因子。我们的前期研究结果提示：口服选择性腺苷转运体抑制剂，可显著改善小鼠阴茎海绵体内腺苷浓度；且病理 状况下，腺苷转运体存在表达异常的现象。因此我们提出假设：干预特定腺苷转运体，致靶细胞内外腺苷浓度改变，介导腺苷信号通路，可促进阴茎康复。为验证此假设，本项目将围绕“生理及病理状况下阴茎腺苷转运体及其亚型的表达及分布”，“选择性腺苷转运体抑制剂在促进阴茎勃起功能改善中的作用”，“利用基因敲除小鼠阐明腺苷转运体靶点在阴茎康复中的机制”等问题开展一系列的基础研究。力争建立一种全新的阴茎康复新疗法，为勃起功能障碍的治疗提供新的思路。

In clinical setting, penile rehabilitation (PR) currently faces insurmountable obstacles, such as poor compliance and uncertain effectiveness. To solve this issue, a brand-new perspective is urgently needed. Former researches from others and our group indicate that adenosine induces penile smooth muscle relaxation and overdosed adenosine causes priapism. Nucleoside transporters play an important role in controlling the intracellular and extracellular concentrations of adenosine. Our previous data shows that oral nucleoside transporter inhibitor can significantly increase the concentrations of adenosine in penis, and the nucleoside transporters are showed abnomarl expressions in pathological conditions. Therefore, we hypothesize: to manipulate the nucleoside transporters, which can increase the concentration of adenosine therefore active its cascade signal pathway, is an effective way to promote the PR. To verify this hypothesis, three specific aims are proposed: (1) to explore the expression and the distribution of all the members of the nucleoside transporter in penis under physical and pathological conditions; (2)to demonstrate the effectiveness of selective nucleoside transporter inhibitor in promoting PR; (3)to delineate the molecular mechanisms of the nucleoside transporter in PR using knock-out mice. The answer to the above aims will provide us with novel therapy in PR.