肾衰宁胶囊对慢性肾脏病合并高磷血症大鼠的药效学研究

目的 研究肾衰宁胶囊对慢性肾脏病合并高磷血症大鼠模型的改善作用。方法 选择90只雄性SD大鼠，腺嘌呤联合高磷饮食诱导慢性肾脏病合并高磷血症大鼠模型，依据血磷水平及肾损伤程度分为模型组（16只）、司维拉姆组（阳性药，掺食法给予3%碳酸司维拉姆片，14只）和肾衰宁低、中、高剂量组（ig给予肾衰宁胶囊400、600、800 mg·kg^-1，低剂量组15只，高、中剂量组分别有16只），另设对照组（正常饲料喂养），连续给药5周。将各组大鼠置于代谢笼中24 h，记录饮水及饮食量，收集各组大鼠24 h尿液及粪便，记录大鼠的尿量、粪便排泄量；试剂盒法测定动物血清磷、钙、肌酐、尿素氮、成纤维细胞生长因子23（FGF-23）、1，25-二羟基维生素D[1，25（OH）₂D]、甲状旁腺激素（PTH）、碱性磷酸酶活力（ALP）水平，计算钙磷乘积；取肾脏称质量、计算肾脏指数，肾脏组织HE、Masson病理染色评价损伤程度；体外磷结合实验检测在pH 3、5、7、8条件下肾衰宁（2.75、5.50、13.75 mg·mL^-1）是否与磷结合。结果 与模型组比较，肾衰宁低、高剂量组日饮食量、24 h排便量、24 h排便颗粒显著升高（P<0.05、0.001），低、中、高剂量组日饮水量显著降低（P<0.05、0.01），高剂量组24 h排尿量显著降低（P<0.05）；低、高剂量组血清磷水平、钙磷乘积显著降低（P<0.01、0.001）；高剂量组血清肌酐水平显著降低（P<0.05），低、高剂量组血清尿素氮水平显著降低（P<0.05、0.01）；各剂量组肾脏外观明显改善，高剂量显著改善肾脏病理损伤程度（P<0.01）；高剂量组FGF-23、PTH、ALP水平显著降低（P<0.05、0.01、0.001），1，25（OH）₂D水平均显著升高（P<0.001）；体外磷结合实验未出现肾衰宁结合磷的现象。结论 肾衰宁胶囊可以改善模型动物的钙磷代谢紊乱，改善肾损伤，调节钙磷代谢相关激素水平。

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.