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Effect Of Hyperphosphatemia On Type Ⅱa Sodium-dependent Phosphate Cotransporter MRNA Expression And The Interference Of Renagel And PFA

Posted on:2005-05-22Degree:MasterType:Thesis
Country:ChinaCandidate:M CengFull Text:PDF
GTID:2144360125451767Subject:Renal disease
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Objective: (l)To investigate if the effect of high phosphorus on intact parathyroid hormone(iPTH) independent of serum calcium, 1,25-(OH)2D3(2)To study the effect of high phosphorus on type IIa sodium-dependent phosphate cotransporter mRNA expression in kidney of uremic rats. (3) To evaluate the interference of Renagel and phosphono-forinic acid (PFA) with type IIa Na-Pi cotransporter.Methods: Male Sprague-Dawley rats underwent 5/6 nephrectomy or sham operation. The animals were then divided into two dietary groups: high-Pi diet(1.2%P)and low-Pi diet(0.2% P) at random.In high-Pi dietary groups,there were six normal rats,six uremic rats nothing treated, six uremic rats treated with Renagel,six uremic rats injected PFA 150mg/kg through intraperitoneal everyday,six uremic rats injected the equivalent volume of physiological saline.In low phosphorus dietary groups,there were six normal rats,six uremic rats nothing treated. Serum ionized calcium, phosphorus, l,25(OH)2D3and iPTH level were detected at the following intervals:2 day,7 day and 14day.The kidney of all rats were removed after they were killed at 14th day.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) was applied to detectthe type Ha Na-Pi cotransporter.Results: (1) Serum P and iPTH levels in uremic rats fed the high-Pi diet(UHP) were significantly higher than low-Pi diet and sham operational rats fed the high-Pi or low-Pi diet (serum P 3.93 ?0.27versus 2.42 ?0.84, 3.07 ?0.64,3.05 ?0.84mmol/L, iPTH 75.50 ?20.19versus30.55 ?2.33,32.98 ?5.37,30.72 ?5.48pg/ml,P<0.05). Meanwhile, there was no significant difference in serum ionized calcium or 1,25-(OH)D(P>0.05) in the four groups mentioned above.(2) Serum P and iPTH levels in Renagel-treated rats were much lower than UHP rats(serum P 3.23 ?0.57 versus3.93 ?0.27 mmol/L, iPTH33.63 ?5.16versus75.50 ?20.19pg/ml, P<0.05). (3)Serum iPTH level was much lower in PFA-treated rats than UHP rats and UHP rats treated with physiological saline (41.73 ?0.19 versus75.50 20.19, 71.09 ?19.36 mmol/L, P <0.05),but there was no difference in serum ionized calcium or 1,25-(OH)2D among the three groups(P>0.05). There was no signigicantly difference in all indexes between the UHP rats and those treated with physiological saline.(4) The expression of type Ha Na-Pi cotransporer mRNA was significantly decreased in high-Pi diet group than low-Pi diet group of uremic rats (1.11 ?.02 versus 1.87 ?.05,P<0.05). (5) The expression of NaPi-2 mRNA was much higher in Renagel-treated rats than UHP rats (NaPi-2 mRNA/ GAPDH mRNA 3.26?.04 versus 1.11?.02, P<0.05).(6)There was no difference of the expreesion of NaPi -2 mRNA between PFA-treated ratsand UHP rats (NaPi-2 mRNA/ GAPDHmRNA 1.09?.02 versus 1.11 ?.02 P>0.05).(7)FEp was much higher in PFA-treated rats than UHP rats(55.51 ?.02 versus37.98?.58%, P<0.05),while it was much lower in Renagel-treated rats than the latter(22.36?.42 versus 37.98?.58%,P<0.05).Conclusions: (l)Hyperphosphatemia is perhaps an independent factor to increase iPTH level independent of serum calcium, 1,25-(OH)2D3. (2)High-Pi diet can reduce the expression of NaPi-2 mRNA of kidney in uremic rats.(3)Renagel can decrease the level of serum P and iPTH.lt can also enhance the expression of NaPi-2 mRNA.(4)PFA is a specific inhibitor of renal Na-Pi cotransporer.lt causes phosphaturia and induce the decrease of iPTH.
Keywords/Search Tags:type IIa Na-Pi cotransporer of kidney, Renagel, high phosphate: uremic rats, intact parathyroid hormone, phosphonoformic acid(PFA)
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