多发性硬化症(MS)主要并发症尿频、尿急等严重影响患者的生活质量，给其带来沉重的心理和经济负担。课题组首次在国际上证实:EP3和EP4受体在实验性自身免疫性脑脊髓炎(EAE)诱发膀胱功能障碍中起重要作用。同时，预实验提示: 随EAE临床评分增加，P2Y6及Panx1的表达较对照组显著增加；且Entpd2抑制剂显著减少EAE组排尿次数，增加平均排尿量。因此，课题组在前期研究、预实验等基础上提出 Entpd2可能调控嘌呤受体P2Y6和Panx1/PGE2/EP3/4通路介导EAE膀胱活动障碍。为此，我们拟通过离体和在体研究特异性调控Entpd2活性，解析其对嘌呤受体P2Y6和Panx1/PGE2 /EP3/4通路分子的相互作用关系，观测阻断关键通路分子对EAE膀胱异常活动的作用，为MS膀胱功能障碍的治疗提供理论基础。

Multiple sclerosis (MS) is the second most common cause of neurogenic bladder, severely impacts the quality of life of MS patient, brings enormous psychological troubles and heavier financial pressures. Our groups have firstly reported that EAE-induced up-regulation of EP3 and EP4 receptors in the bladder was accompanied via bladder dysfunction through constructing the neurogenic bladder model for MS bladder dysfunction through inducing by experimental autoimmune encephalomyelitis (EAE). However, EAE had no significant effect on EP1 and EP2 receptors. Moreover, PGE2 and agonists/antagonists of EP3 and EP4 receptors significantly affected bladder dysfunction in EAE mice. Meanwhile, the results of preliminary experiment implied that EAE induced the upregulation of P2Y6 receptors and Panx1 with a concomitant increase in disease severity, the EAE clinical score was significantly decreased in Entpd2 antagonist group. Based on our results of previous study, results of preliminary experiment, and the progress of bladder dysfunction, our groups speculate Entpd2, P2Y6, Panx1/PGE2/EP3/4 pathway participate in the regulation of bladder dysfunction for MS. Respecting, our groups would confirm the function of Entpd2 in regulating the bladder dysfunction through selectively inhibiting the Entpd2 activity and purinergic receptors P2Y6 and Panx1/PGE2/EP3/4 pathway, provide the experiment basis for bladder dysfunction of MS.