细胞内物流系统与高血压发生密切关联。我们前期发现线粒体外膜转运蛋白TSPO在自发性高血压大鼠（SHR）近曲小管（RPT）中表达增高；TSPO抑制剂发挥降血压、促尿钠排泄效应；该作用经由AT1R介导，抑制TSPO降低肾脏AT1R表达。进一步研究发现肾脏TSPO与VDAC1存在共连接，其在SHR中增强；敲低TSPO后VDAC1在线粒体中表达降低、在细胞质中则显著升高。鉴于VDAC1可影响NF-κB活性，后者是AT1R关键转录因子，我们推测“高血压状态下，肾脏TSPO表达增高，增强其与VDAC1结合能力，影响VDAC1从线粒体膜向胞浆释放，减弱其对NF-κB的调节，后者活性增加，引起AT1R表达上升，导致钠排泄障碍和高血压发生”。本研究基于前期工作，拟利用TSPO敲除或转基因小鼠、SHR及相应RPT细胞，研究肾脏TSPO在高血压发生中的作用和机制，为阐明TSPO在高血压发生中的作用提供理论依据。

Intracellular logistics system is associated with hypertension. Our preliminary data showed that the expression of translocator protein (TSPO) was increased in the renal proximal tubule (RPT) in the spontaneously hypertensive rat (SHR); treatment of TSPO inhibitor decreased blood pressure and increased natriuresis; above effects were mediated via AT1R because we found that TSPO inhibiton decreased AT1R expression. Our studies also showed that TSPO co-immunoprecipitated with Voltage-dependent anion channel 1 (VDAC1), which was increased in the kidney of SHR; TSPO knockdown decreased mitochondrial VDAC1 expression, but increased cytoplasmic VDAC1 expression. VDAC1 can regulate the activity of NF-κB, which is the key transcription factor of AT1R. We suppose that in the hypertensive status, TSPO expression is enhanced, which increases the direct interaction with VDAC1, inhibits VDAC1 releasing from mitochondrion to cytoplasm, leads to increased NF-κB activity and AT1R expression. Based on our preliminary studies, in this project, we will study the renal TSPO in the pathogenesis of hypertension and its mechanisms in the TSPO knockout mice, transgenic mice, SHR and RPT cells.