刺激肾脏多巴胺受体具有排钠效应，多巴胺D5受体(D5R)对多巴胺亲和力最强，具有内源激活，胞内转运方式特殊等特点，备受关注。我们发现高血压状态下D5R功能丧失，这与其胞内转运异常有关，但导致该异常的原因尚不清楚。SNXs在受体转运中发挥核心作用，我们发现SNX1-/-小鼠血压增高，伴多巴胺D1R/D5R介导的尿钠排泄下降。由于SNX1在结构上只与D5R（不与D1R）结合；且高血压病人肾近曲小管（RPT）细胞SNX1表达下降，推测SNX1通过影响D5R胞内转运进而影响其排钠功能，高血压状态下SNX1表达下降是导致D5R尿钠排泄功能丧失的原因。基于前期工作，用SNX1/D1R双敲除小鼠及其分离的RPT细胞研究SNX1对D5R功能的调节及D5R胞内转运的作用机制；探索增加高血压大鼠肾脏SNX1表达后在恢复D5R功能与降血压中的作用，为阐明SNX1对D5R的调节和高血压防治提供理论依据和防治靶点。

Stimulation of dopamine receptors leads to renal sodium excretion. In recent years, studies pay more attention to the benefits of the dopamine D5 receptor (D5R) for its three distinctive features: the strongest affinity to dopamine, the constitutive activity and specific trafficking properties. Our previous study found that the dysfunction of D5R in renal proximal tubule cells (RPTCs) from hypertensive (HT) is related with its abnormal trafficking, but the reason still needs to be determined. Sorting nexins (SNXs) play an important role in the sorting of receptors. SNX1 interacts with D5R, but not D1R; SNX1 expression is decreased in RPTCs from HT, so we speculate that SNX1 regulates the sorting of D5R, which affects its function of natriuresis; however, the decreased SNX1 expression leads to the impaired D5R-mediated natriuresis. Based on our previous studies, we will study the regulation of SNX1 on the function of D5R, the regulatory mechanism of SNX1 on the D5R trafficking, and the restored D5R function and trafficking in SNX1-rescued SHR kidney and PRTCs. Our study will provide the theory basis for the regulation of SNX1 on D5R in the pathogenesis of hypertension.