Regucalcin介导的细胞膜Ca2+-ATP酶调控在草酸钙结石形成中的作用及机制研究

肾小管上皮细胞内钙稳态的破坏被认为在草酸钙结石形成过程中具有重要作用，但具体机制不明。Regucalcin（RGN）是新近发现的一种钙结合蛋白。我们前期研究发现：草酸钙晶体不但可以明显诱导肾小管上皮细胞RGN表达下调，而且草酸钙结石大鼠肾组织中RGN的表达也降低，尤其在晶体粘附处明显，提示RGN参与了草酸钙晶体的粘附和结石形成。由于RGN可以调控细胞膜Ca2+-ATPases（PMCA）的表达及活性，而PMCA可以通过调控细胞内钙的转运导致细胞损伤，进而影响晶体粘附。我们推测RGN可能通过调控PMCA破坏细胞内钙稳态，参与了晶体粘附和结石形成过程。本研究拟在检测RGN对草酸钙晶体诱导的细胞损伤和晶体粘附影响的基础上，通过构建肾脏沉默和过表达RGN大鼠，研究RGN在草酸钙结石形成中的作用及可能机制，为明确草酸钙结石发病机制提供新的实验依据，为草酸钙结石的预防提供新的干预靶点。

The disorder of calcium homeostasis in the epithelia of renal tubules is an important role in calcium oxalate stone formation, however, the mechanism is still unknown. Regucalcin(RGN) is a new calcium-binding protein, which plays a pivotal role in maintaining the intracellular calcium homeostasis. Our former study indicated that RGN was down-regulated in epithelia of renal tubules after treated with COM crystal. In calcium oxalate stone rat model, RGN was also significantly down-regulated in renal tissue, especially in those tissue surrounded by the calcium oxalate crystals. These results disclosed that RGN was involved in the pathogenesis of cellular damage and calcium oxalate stone formation. It is already known that RGN could regulate the expression and activity of plasma membrane Ca2+ ATPases (PMCA), whereas Ca2+ ATPases (PMCA) has been involved in cell injury and regulate the level of intracellular calcium, which will induce the adhesion of calcium oxalate crystals to the epithelia of renal tubules, and latterly, the calcium oxalate stone will be formed. . According to our former results and reported literatures, we suspect that RGN was involved in process of calcium oxalate stone formation by regulating the expression and activity of PMCA. In this study we try to explain the possible effect and mechanism of RGN on the formation of calcium oxalate stone. First, the role of RGN on cellular damage and crystal retention induced by calcium oxalate crystals was examined. Furtherly, the rat model with the RGN silence or over-expression in the kidney was established, which was involved in the study to confirm the role of RGN in calcium oxalate stone formation. . Our study aims to providing an experimental basis for the pathogenesis of oxalate stone stone formation and a new intervention strategy for the prevention and treatment of calcium oxalate stone.