糖尿病性勃起功能障碍(DED)是糖尿病常见早期合并症之一，DM患者ED发病率高达75％，严重危害身心健康及家庭和谐。前期研究发现DED与阴茎内皮和神经病变有关，利用胰岛素降血糖治疗却不能完全阻断DED病理变化。这些结果提示糖尿病代谢记忆可能在DED发生发展中具有重要作用，由于代谢记忆过程中糖基化终末产物（AGEs）的不可逆性，即使高血糖被纠正，AGEs也继续在组织中累积，并引发后续效应造成脏器损伤，因此探明AGEs发生发展机理并研究调节代谢记忆的药物治疗靶点对防治糖尿病合并症具有重要科学意义。本研究构建糖尿病动物模型，采用免疫缺陷小鼠异种移植体内组织培养技术来彻底改变糖尿病的病理微环境，观察AGEs及受体对DED阴茎内皮和神经病理学变化的影响以及对下游不同信号通路相关基因和蛋白的分子生物学变化，阐明AGEs及受体在DED发生发展中分子生物学机制和药物作用靶点，为防治DED及新药开发奠定理论

Diabetic erectile dysfunction (DED) is one of the common complications of diabetes with a prevalence of about 75% in diabetic patients. DED does great harm to health and family harmony of DM patients. Previous studies have suggested that damaged endothelium and nerves were associated with DED, but its pathological changes could not be reversed by the insulin adoption. We hypothesis that metabolic memory may play an important role in the development of DED. AGEs generated in the process of metabolic memory can not be affected by the glucose level. Accumulated AGEs leads to the pathological injury of the tissue. Research about the mechanisms in generation of AGEs and drugs affected metabolic memory may be of great value in the treatment of DM. We will set animal model of DM, change its pathological microenvironment by tissue cultural in immune-knock down mice, and study AGEs's affect on endothelium and nerves in penis. The associated signal pathway and change of gene or protein expression will also be explored. All these research will lay the basis of the treatment of DED and the drug development.