Effects Of Valsartan On The Secondary Hyperparathyroidism And The Renal Fibrosis From Uremic Rats

BackgroudParathyroid belongs to extremely low differentiated tissues, the life cycle of normal human’s PG is20years, the rat’s PG cell survivals two years. Normal parathyroid cell are characterized by an extremely low turnover. However they still remain the proliferative ability if they were stimulated. In human subjects, parathyroid hyperplasia is initiated by hypocalcemia and phosphorus retention and becomes more severe as the result of calcitriol deficiency in response to chronic renal failure. Parathyroid growth progresses through several stages from diffuse hyperplasia to nodular hyperplasia and to formation of adenomas. COX-2expression was significantly increased in parathyroid glands of SHPT patients. Ang II is associated with the increased expression of COX-2. The present studies examined the effects of valsartan and celecoxib on the renal function and the hyperplasia of parathyroid glands.Methods5/6-nephrectomized (Nx) and sham operated rats were assigned to five groups:(1) Sham-operated+normal phosphorus diet group (Sham-NP group, n=10);(2)5/6-nephrectomized+normal phosphorus diet group (Nx-NP group, n=10);(3)5/6-nephrectomized+high phosphorus diet group (Nx-HP group, n=10);(4) Valsartan group (Val group, n=10);(5) Celecoxib group (Cel group, n=10). Serum creatinine, BUN, calcium (Ca),phosphorus(P), and serum parathormone (iPTH),1,25(OH)2D3levels were determined at week4%、16after operation. All the animals were killed at the end of experiment. The size of parathyroid glands and the renal histopathological changes were observed by HE and Masson staining. The expression of COX-2was determined by immunohistochemistry.ResultsThe level of serum iPTH in four Nx groups were significantly increased than in Sham group (P<0.01), valsartan and celecoxib decreased serum iPTH levels. The score of GSI and TIS in four Nx groups were significantly increased than in Sham group (P<0.01), Valsartan improved the renal fibrosis of uremic rats.The size of parathyroid glands/weight in Nx-HP group was the most significantly increased valsartan and celecoxib decreased the maximum size of parathyroid glands. The levels of COX-2expression in kidney and parathyroid glands were greatly increased in four Nx groups.Conclusion5/6-nephrectomized plus high phosphorus diet can successfully foud SHPT model.Valsartan can relieve the renal fibrosis and help to suppress the hyperplasia of parathyroid glands in uremic rats.