| Objective:High phosphorus diet is a very important reason of secondary hyperparathyroidism due to chronic renal failure. Diet calcium is the main factor that disturbs the absorption of phosphorus in intestinal tract and the excretion of kidney. Now clicinal guideline recommend CRF patients to supplement calcium for treatment.Is there any influence on SHPT due to high blood phosphate? in addition,Now CRF patients are recommended to have low phosphate diet in order to improve SHPT clinically, but whether there is any effect for different diet calcium to the inhibition of low phosphate diet on SHPT,we are not clear right now.the objective of our study are(1)sudy the effect of diet calcium to SHPT due to high blood phosphate associated high mortality and mechanism;(2)study the effect of restrict diet calcium to the inhibition of low phosphate diet to SHPT.Methods:S-D rats received5/6nephrectomy to make chronic renal failure models, sham group just divested the envelop,and then2weeks after make uremic model,give them different level calcium and phosphation feedstuff (phosphation:highl.2%,low0.2, normal0.9%;calcium:highl.6%,lowl.0%, normal0.5%),they were divided into high phosphorus-calcium group (group HPHCa, n=8), high phosphorus normal calcium group (group HPNCa, n=8), low phosphorus-calcium group (group LPLCa,n=7), low phosphorus normal calium group (group LPNCa,n=7). Normal phosphorus-calcium group (group NPNCa, n=16), Sham group received normal phosphate and calcium diet(n=8). Every4weeks, the blood and urine was collected, we test blood calcium,phosphate,iPT、FGF23,1,25(OH)2D3and creatine.Also the density of urine protein and creatine,calcium and phosphate. At week24,the rats were sacrificed, get the parathyroid, observe the change of histology, observe the expression of PCNA,VDR, FGFR1c、Klotho and CaSR and p-ERK1/2using an immunohistochemical procedure.Results:(1)The survival number in HPHCa group、HPNCa group、LPLCa group、 LPNCa group、NPNCa group、Sham group were8、3、4、6、8、8. The difference among groups is obvious, survival rate of group HPNCa and LPLCa obviouly lowe than group HPHCa and group Sham (p<0.01,0.05). survival rate of group HPNCa is obviously lower than group LPNCa(p<0.05).(2) Campared with group sham,blood phosphate,iPTH and FGF23are higher,1,25(OH)2D3is lower,parathyroid area/body weight,express of PCNA increased. VDR、FGFRl、Klotho and CaSR decreased. p-ERK1/2increased in group NPNCa(p<0.05), HPNCa was more obvious(p<0.05).but the express ofp-ERK1/2decrease (p<0.01). as well, compared with HPNCa group,blood phosphate,iPTH,FGF23decreased(p<0.01), degree of hyperplasia in parathyroid is less.p-ERK1/2and CaSR increased obviously in group HPHCa.(3) Campared with group NPNCa, blood phosphate,iPTH,FGF23of group LPNCa decreased obviously,blood calcium increase obviously(p<0.01). parathyroid area/body weight,express of PCNA, p-ERK1/2increaser(p<0.05).campared with group LPNCa,blood calcium and phosphation,iPTH and FGF23are lower,1,25(OH)2D3increased, parathyroid area/body weight,expression of PCNA and p-ERK1/2in group LPLCa are lower (p<0.05).(4) correlation analysis shows that,above index,just blood phosphate and parathyroid p-ERK1/2in uremic rats have obvious correlation with the survival rate (r=-0.54、0.43, p<0.05).Conclusion:Uremic rats have parathyroid hyperplasia together with functionality receptors(VDR、FGFR1、Klotho and CaSR)low express, enhance the diet calcium can improve the hyperplasia of parathyroid due to high phosphate diet,decreased the morality rate.and deficiency of diet calcium can increase the morality rate of low phosphate diet rats;higher blood phosphate and low express of parathyroid p-ERK1/2are important danger factors for the increase of morality rate in uremic rats. |
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