[關(guān)鍵詞]
[摘要]
目的 研究腎衰寧膠囊對(duì)慢性腎臟病合并高磷血癥大鼠模型的改善作用。方法 選擇90只雄性SD大鼠,腺嘌呤聯(lián)合高磷飲食誘導(dǎo)慢性腎臟病合并高磷血癥大鼠模型,依據(jù)血磷水平及腎損傷程度分為模型組(16只)、司維拉姆組(陽性藥,摻食法給予3%碳酸司維拉姆片,14只)和腎衰寧低、中、高劑量組(ig給予腎衰寧膠囊400、600、800 mg·kg-1,低劑量組15只,高、中劑量組分別有16只),另設(shè)對(duì)照組(正常飼料喂養(yǎng)),連續(xù)給藥5周。將各組大鼠置于代謝籠中24 h,記錄飲水及飲食量,收集各組大鼠24 h尿液及糞便,記錄大鼠的尿量、糞便排泄量;試劑盒法測定動(dòng)物血清磷、鈣、肌酐、尿素氮、成纖維細(xì)胞生長因子23(FGF-23)、1,25-二羥基維生素D[1,25(OH)2D]、甲狀旁腺激素(PTH)、堿性磷酸酶活力(ALP)水平,計(jì)算鈣磷乘積;取腎臟稱質(zhì)量、計(jì)算腎臟指數(shù),腎臟組織HE、Masson病理染色評(píng)價(jià)損傷程度;體外磷結(jié)合實(shí)驗(yàn)檢測在pH 3、5、7、8條件下腎衰寧(2.75、5.50、13.75 mg·mL-1)是否與磷結(jié)合。結(jié)果 與模型組比較,腎衰寧低、高劑量組日飲食量、24 h排便量、24 h排便顆粒顯著升高(P<0.05、0.001),低、中、高劑量組日飲水量顯著降低(P<0.05、0.01),高劑量組24 h排尿量顯著降低(P<0.05);低、高劑量組血清磷水平、鈣磷乘積顯著降低(P<0.01、0.001);高劑量組血清肌酐水平顯著降低(P<0.05),低、高劑量組血清尿素氮水平顯著降低(P<0.05、0.01);各劑量組腎臟外觀明顯改善,高劑量顯著改善腎臟病理損傷程度(P<0.01);高劑量組FGF-23、PTH、ALP水平顯著降低(P<0.05、0.01、0.001),1,25(OH)2D水平均顯著升高(P<0.001);體外磷結(jié)合實(shí)驗(yàn)未出現(xiàn)腎衰寧結(jié)合磷的現(xiàn)象。結(jié)論 腎衰寧膠囊可以改善模型動(dòng)物的鈣磷代謝紊亂,改善腎損傷,調(diào)節(jié)鈣磷代謝相關(guān)激素水平。
[Key word]
[Abstract]
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.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]