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目的 研究肾组织钠/二羧基转运蛋白1(SDCT1)与低枸橼酸尿的关系以及枸橼酸钾的干预作用,探讨肾结石发病的分子机制和防治措施。方法 雄性Wistar大鼠分为对照组、肾结石组及枸橼酸钾干预组。血、尿枸橼酸和草酸采用酶法测定,Northern blot检测大鼠肾组织SDCT1mRNA水平的改变,免疫组织化学观察SDCT1在肾组织的分布及表达变化。结果 与对照组比较,肾结石组第3天尿草酸水平显著升高,枸橼酸水平显著降低,同时肾组织SDCT1mRNA及其蛋白水平上调。第7天SDCT1mRNA及其表达产物增加更为显著,同时尿枸橼酸水平进一步降低,尿钙排泄显著增加,87.5％大鼠有中-大量的草酸钙结石形成。第14天上述改变更为明显,结石形成率达100％。枸橼酸钾干预组各时间点尿草酸水平与肾结石组差异无显著性意义,但尿枸橼酸水平显著高于肾结石组及对照组,肾组织SDCT1mRNA及蛋白表达显著低于肾结石组,与对照组差异无显著性意义;结石形成率显著低于肾结石组;肾小管扩张、炎细胞浸润等病变也明显减轻。结论 肾组织SDCT1表达上调可能是低枸橼酸尿的重要原因,与肾结石的形成有密切关系。枸橼酸钾可下调肾结石大鼠肾组织SDCT1的表达,对肾结石的形成具有明显的干预作用。
Objective To study the relationship between renal tissue sodium / dicarboxy-transport protein 1 (SDCT1) and low citrate urine and the intervention of potassium citrate so as to explore the molecular mechanism and prevention and cure measures of kidney stones. Methods Male Wistar rats were divided into control group, kidney stone group and potassium citrate intervention group. Urinary citrate and oxalic acid were determined by enzymatic method. Northern blot was used to detect the changes of SDCT1mRNA in renal tissue. Immunohistochemistry was used to observe the distribution and expression of SDCT1 in renal tissues. Results Compared with the control group, the level of urinary oxalate in the kidney stones group was significantly increased on day 3, the level of citric acid was significantly decreased, and the level of SDCT1 mRNA and protein in the kidney tissues was also increased. On the 7th day, the expression of SDCT1mRNA and its expression products increased more significantly. At the same time, urinary citrate level was further decreased and urinary calcium excretion was significantly increased. 87.5% of rats had moderate-large calcium oxalate stones formation. On the fourteenth day, the above changes were more obvious. The rate of stone formation reached 100%. There was no significant difference between the levels of urinary oxalate in the potassium citrate intervention group and the nephrolithiasis group, but the urinary citrate level was significantly higher than that of the nephrolithiasis group and the control group. The expression of SDCT1 mRNA and protein in the kidney tissue was significantly lower than that of the nephrolithiasis group , No significant difference with the control group; stone formation rate was significantly lower than the group of renal stones; tubular dilatation, inflammatory cell infiltration and other lesions were significantly reduced. Conclusion Upregulation of SDCT1 expression in renal tissue may be an important cause of low citrate aciduria and is closely related to the formation of kidney stones. Potassium citrate can down-regulate the expression of SDCT1 in renal tissue of kidney stone rats, which has a significant intervention on the formation of kidney stones.