磷对慢性肾衰鼠甲状旁腺增生的独立作用和膦甲酸钠干预的研究

Independent Role of Phosphorus on Parathyroid Gland Hyperplasia in Chronic Renal Failure Rats

目的:探讨磷对甲状旁腺(PTG)增生的独立作用;利用磷钠转运体(NPCs)的抑制剂膦甲酸钠(PFA)探讨PTG细胞感受胞外磷的可能作用机制。方法:配制高磷(含磷1.2％,钙1.6％)、低磷(含磷0.2％,钙0.5％)大鼠饲料。6组大鼠:①低磷假手术组(NLP);②低磷慢性肾衰组(ULP);③高磷假手术组(NHP);④高磷慢性肾衰组(UHP);⑤UHP+PFA组,每日腹腔注射PFA150 mg/kg体重;⑥UHP+生理盐水(NaCl)组,每日腹腔注射与PFA等体积的生理盐水。共喂饲14天。第2、7、14天分别检测血磷、离子钙(iCa)、肌酐(Cr)、血清全段甲状旁腺激素(iPTH),并在第14天测血1,25-(OH)2D3;免疫组化检测PTG核增殖抗原(PCNA)。结果:各组1,25-(OH)2D3、iCa均差异无显著性(P>0.05)。UHP组血磷、iPTH明显高于ULP组(P<0.05)。UHP+PFA组iPTH明显低于UHP+NaCl组(P<0.05),第14天明显低于UHP组(P<0.05),3组间血磷无统计学差别。UHP组PCNA表达量0.33±0.07明显大于ULP组0,22±0.06(P<0.05),UHP+PFA组PCNA 0.28 4±0.06低于UHP组(P<0.05),UHP+NaCl组PCNA 0.32+0.07与UHP组差异无显著性。结论:不依赖于血iCa、1,25-(OH)2D3变化,高血磷促进、低血磷抑制大鼠PTG增生和PTH分泌。磷可能通过NPCs作用于PTG细胞,PFA有治疗前景。

Phosphonoformic acid(PFA) can competitively bind to sodium-dependent phosphate(Na/P) cotransporter. In this study, we examined the direct role of phosphorus (P) on the development of parathyroid gland hyperplasia in chronic renal failure rats and explored whether the parathyroid gland (PTG) was sensitive to extracellular inorganic P by the Na/P cotransporter. Methods: Male Sprague-Dawley rats underwent 5/6 nephrectomy (uremic rats) or sham operation, and were divided into two dietary groups(1. 2% P and calcium(Ca) 1. 6% diet; 0. 2% P and Ca 0. 5% diet) respectively. In high-P dietary(HPD) uremic rats, six were intraperitoneally injected with PFA 150 mg/kg, six were injected with equivalent dissolvent of PFA and six were not treated. Blood was taken for measurement of creatinine, ionized calcium(iCa), P, 1, 25-(OH)2D3, and intact parathyroid hormone (PTH) at the 2nd day, 7 th day and 14 th day. PTG were removed for immunohistochemistry analysis of proliferating cell nuclear antigen(PCNA) . Results: Serum P and PTH levels in uremic rats fed with HPD were significantly higher than those fed with low-P dietary (LPD), but there were no significant differences in serum iCa and 1, 25-(OH)2D3 levels. Serum PTH levels of PFA-treated HPD uremic rats were lower than those of HPD uremic rats without PFA treatment, but no significant differences were found in serum iCa, P and 1, 25-(OH)2D3. There was no significant difference in serum P among HPD uremic rats treated with or without PFA, LPD uremic rats. The levels of PCNA in PTG were lower in PFA-treated HPD uremic rats than those in HPD uremic rats without PFA treatment(0. 29 ±0. 05v0. 33±0. 07, P = 0. 04). Conclusion: High serum P accelerates and low serum P prevents the development of PTG hyperplasia and secondary hyperparathyroidism in uremic rats independent of serum iCa and 1, 25- (OH) 2D3. PFA may prevent the develpment of PTG hyperplasia and secretion of PTH by the Na/P cotransporter.