人钠/二羧基转运蛋白1在肾组织的表达变化及其与肾结石发病的关系

The change of human Na^+/dicarboxylate co-transporter 1 expression in the kidney and its relationship with pathogenesis of nephrolithiasis

目的 研究肾组织钠 /二羧基转运蛋白 1(hNaDC1)表达变化与肾结石发病的的关系。方法 85例肾结石患者分为、尿枸橼酸正常结石组和低枸橼酸尿结石组。并设 5 0例对照为非结石患者。采用RT PCR及Northern印迹法检测其中部分肾结石患者肾组织的hNaDC1mRNA水平 ;免疫组化检测hNaDC1蛋白表达的变化 ;常规生化方法测定血、尿枸橼酸、草酸等生化指标。结果 低枸橼酸尿结石组结石复发率 (36 .1% ) ,显著高于尿枸橼酸正常结石组 (16 .3% ,P <0 .0 1)。hNaDC1mRNA在正常肾组织中有表达 ,分布于近端肾小管刷状缘 ;低枸橼酸尿结石患者hNaDC1mRNA/18sRNA比值 (0 .6 5± 0 .2 1)显著高于对照组 (0 .36± 0 .11,P <0 .0 1) ;而尿枸橼酸正常结石患者 (0 .4±0 .13)与对照组比较差异无显著意义 (P >0 .0 5 ) ;低枸橼酸尿结石组hNaDC1蛋白表达也显著高于对照组及尿枸橼酸正常结石组 (P <0 .0 1) ,而后两组间差异无显著意义 (P >0 .0 5 )。低枸橼酸尿结石组尿pH值、尿钠水平显著低于尿枸橼酸正常结石组和对照组 ;尿钙、尿草酸水平均显著高于对照组 ,与尿枸橼酸正常结石组无显著差异。结论 肾组织hNaDC1表达上调可能是低枸橼酸尿的重要原因 。

Objective To study the change of Na +/dicarboxylate co transporter l expression in the kidney and its relationship with nephrolithiasis. Methods 50 volunteers and 85 patients with nephrolithiasis were divided into 3 groups: control, nephrolithiasis with normal urine citrate, and nephrolithiasis with hypocitraturia. The expression of hNaDC1 mRNA in kidney was determined by RT PCR or Northern blotting, the change of hNaDC1 protein abundance were measured by immunohistochemical staining with anti hNaDC1 antibody among part of these patients and volunteers. The plasma and urinary biochemical parameters, such as citrate, oxalate, uric acid and calcium etc., were analyzed by routine chemical methods. Results The recurrence rate of nephrolithiasis in the group of patients with hypocitraturia was 36.1%, significantly higher than the recurrence rate of 16.3% in the group of patients with normal urine citrate ( P <0.01). hNaDC1 was expressed in the normal kidney, localized in the striated border of renal proximal tubule. However, it was expressed highly in the kidneys of patients with hypocitraturia. The ratio hNaDC1 mRNA/18sRNA in the patients with hypocitraturia was 0.65±0.21, significantly higher than that in the controls (0.36±0.11, P <0.01). The ratio hNaDC1 mRNA/18sRNA in the patients with normal urine citrate was not significantly different from that in the controls ( P >0.05). The urine pH and urine sodium were significantly lower in the patients with hypocitraturia than in the other two groups. The levels of urine calcium and urine oxalate were significantly higher in the patients with hypocitraturia than in the controls, and were not different from those in the patients with normal urine citrate. Conclusion The upregulation of hNaDC1 mRNA and protein abundance in the kidney may be an important cause of hypocitraturia, which might be related with the occurrence and recurrence of nephrolithiasis.