膦甲酸钠对尿毒症大鼠甲状旁腺激素及肾脏Ⅱa型钠-磷协同转运体的影响

Effect of PFA on PTH and expression of type Ⅱa sodium-dependent phosphate cotransporter in the kidneys of uremic rats

目的研究膦甲酸钠(PFA)对尿毒症大鼠全段甲状旁腺激素(iPTH)及肾脏Ⅱa型钠磷协同转运体(NaPi2)mRNA表达的影响。方法36只SD大鼠随机分为6组,每组6只:(1)尿毒症高磷饲料组(UHP);(2)尿毒症低磷饲料组(ULP);(3)尿毒症高磷饲料PFA治疗组(UHP+PFA组);(4)尿毒症高磷饲料氯化钠组(UHP+NaCl);(5)假手术高磷饲料组(NHP);(6)假手术低磷饲料组(NLP)。用5/6肾大部切除术构建尿毒症大鼠模型,分别予高磷(含磷1.2%)或低磷饲料(含磷0.2%),测定第2、7、14天血离子钙(iCa)、磷(P)、iPTH,第14天测血1,25(OH)2D3,RTPCR法检测NaPi2在肾脏的表达。结果1组较2、5、6组血P及iPTH明显增高(P<0.05),4个组血iCa、1,25(OH2)D3无明显差异(P>0.05);3组iPTH明显低于1、4组(P<0.05);1组较2组肾NaPi2mRNA表达明显减少(P<0.01);3组与1组相比,NaPi2mRNA表达无变化(P>0.05),但尿磷酸盐排泄分数明显增高(P<0.05)。结论高磷血症是促进尿毒症大鼠iPTH增高、不受钙和1,25(OH)2D3影响的独立因素;PFA抑制NaPi2转运体,增加尿磷酸盐排泄,降低iPTH。

Objective To investigate the effect of phosphonoformic acid (PFA)on PTH and type Ⅱa Na-Pi cotransporter(NaPi-2)in uremic rats.Methods Thirty-six male Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation.The rats were randomly divided into six groups.The uremic rats in group 1 were treated with high-Pi diet(UHP,1.2%P),in group 2 with low-Pi diet(ULP,0.2%P),in group 3 with PFA(UHP+PFA),in group 4 with physiological saline(UHP+NaCl),in normal controls(group 5)with high-Pi diet(NHP),and in normal rats(group 6)with low-Pi diet(NLP).Serum ionized calcium,phosphorus,1,25-(OH) 2D 3,and iPTH were detected on the 2nd,7th and 14th day.RT-PCR was applied to detect NaPi-2.Results Serum P and iPTH levels in group 1 were significantly higher than those in group 2,5,6(P<0.05).Meanwhile,there was no significant difference in serum ionized calcium or 1,25-(OH) 2D 3(P>0.05)among above four groups.Serum iPTH level was much lower in group 3 than that in group 1 and 4(P<0.05).The expression of NaPi-2 mRNAwas significantly decreased in group 1 than that in group 2(P<0.01).There was no difference in the expression of NaPi-2 mRNA between group 3 and 1(P>0.05),but FEP was much higher in group 3(P<0.05).Conclusion Hyperphosphatemia may be a factor to increase iPTH level independent of serum calcium,1,25-(OH) 2D 3.PFA is a specific inhibitor of NaPi-2,which causes phosphaturia and induces a decrease of iPTH.