Pharmacological evaluation of Shenshuaining Capsules in treatment of chronic kidney disease coupled with hyperphosphatemia
Objective To explore the pharmacological effects of proprietary Shenshuaining Capsules in a rat model of chronic kidney disease with hyperphosphatemia induced by adenine combined with high-phosphate diet.Methods Ninety male SD rats were selected to induce a chronic kidney disease complicated with hyperphosphatemia rat model through a combination of adenine and high phosphorus diet.Based on blood phosphorus levels and degree of renal injury,they were divided into a model group(16 rats),a sviram group(positive drug,administered with 3％carbonated sviram tablets by gavage,14 rats),and a Shenshuaining Capsules low,medium,and high dose group(400,600,800 mg·kg-1,15 rats in the low dose group,and 16 rats in the high and medium dose groups,administered with ig),set up a control group(fed with normal feed)and administer continuously for five weeks.Placed each group of rats in a metabolic cage for 24 hours,recorded their water and dietary intake,collected their urine and feces for 24 hours,and record their urine and fecal excretion.The reagent kit method was used to measure the levels of animal serum phosphorus,calcium, creatinine, urea nitrogen, fibroblast growth factor 23 (FGF-23), 1,25-dihydroxyvitamin D [1,25 (OH)2 D], parathyroid hormone (PTH), and alkaline phosphatase activity (ALP), and calculate the calcium phosphorus product. Weighed the kidney,calculated the kidney index, and evaluated the degree of injury by HE and Masson pathological staining of the kidney tissue. In vitro phosphorus binding experiments were conducted to detect whether Shenshuaining Capsules (2.75, 5.50, 13.75 mg·mL-1) binds to phosphorus under pH 3, 5, 7, and 8 conditions. Results Compared with the model group, the daily food intake, 24-hour defecation volume, and 24-hour defecation particles in the low and high-dose groups of Shenshuaining Capsules significantly increased (P ＜0.05,0.001), while the daily water intake in the low, medium, and high-dose groups significantly decreased (P ＜ 0.05, 0.01), and the 24-hour urine output in the high-dose group significantly decreased (P ＜ 0.05). The serum phosphorus level and calcium phosphorus product were significantly reduced in the low and high dose groups (P ＜ 0.01, 0.001). The serum creatinine level significantly decreased in the high-dose group (P ＜ 0.05), while the serum urea nitrogen level significantly decreased in the low and high-dose groups (P ＜ 0.05, 0.01). The appearance of the kidneys in each dose group was significantly improved, while high doses significantly improved the degree of renal pathological damage (P ＜ 0.01). The levels of FGF-23, PTH, and ALP in the high-dose group were significantly reduced (P ＜ 0.05, 0.01, 0.001), while the levels of 1, 25 (OH)2D were significantly increased (P ＜ 0.001).In vitro phosphorus binding experiment did not show any phenomenon of Shenshuaining Capsules binding phosphorus. Conclusion Shenshuaining Capsules can improve calcium-phosphorus metabolism and kidney injury in model animals. Shenshuaining Capsules has obvious pharmacological effects on chronic kidney disease coupled with hyperphosphatemia in rats.
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