中国现代中药2019，Vol.21Issue(1)：62-67,70,7.DOI:10.13313/j.issn.1673-4890.20180703001
白头翁皂苷B4对实验性急性肾功能损伤的保护作用
Protective Effect of Anemoside B4 from Experimental Acute Renal Damage in Animal
摘要
Abstract
Objective: To investigate the protective effect of Pulsatilla saponin B4 on acute renal injury and acute toxicity in mice. Methods: In vitro, the cell experiments were performed to induce HEK293 injury model by LPS, and B4 was used for 24 and 48 hours. MTT assay was used to detect the activity of cells and the expression of inflammatory factors by q PCR to observe the effect of B4 on renal cell injury. The animal experiments were conducted in rats and mice. In pharmacological study, rats or mice were given glycerol, cisplatin, and lipopolysaccharide (LPS) respectively for acute renal injury. B4 was injected into the caudal vein at different doses. After given for a certain period of time, orbital blood was collected and the serum was separated. Serum BUN, creatinine (Cre), total protein (TP) and rat's urinary protein in rats were determined to evaluate the effect of B4 on the renal damage. In the acute toxicity, mice were injected intravenously with different doses of B4 for2 weeks. According to the death, the half-lethal dose (LD50) was calculated. Results: B4 could increase the activity of injured renal cells and down-regulate the expression of inflammatory factor TNF-α. It also inhibit the increase of serum BUN, Cre induced by cisplatin and LPS caused by increased significantly. At the same time, B4 with high dose (2. 5 mg·kg-1) could also significantly reduce rat urine protein concentration. Its effective dose were 1. 25-2. 5 mg·kg-1in rats, and 5-10 mg·kg-1in mice. The LD50 for intravenous administration of B4 to mice was 3. 36 g·kg-1and the 95％ confidence limit was 3. 34 to 3. 37 g·kg-1. And therefore, the clinical safety index of B4 was 168 (3. 36/0. 02) based on the maximum dose of 20 mg·kg-1in mice, showing B4 has a high clinical safety range. Conclusion: B4 has definite protective effect on experimental acute renal impairment, and meanwhile its large clinical safety index suggests that this compound has a good prospects for the development of new drugs.关键词
白头翁皂苷B4/肾损伤/急性毒性/人胚肾细胞HEK293/脂多糖/甘油/顺铂Key words
nemoside B4/renal damage/acute toxicity/human embryonic kidney cells HEK293/LPS/glycerin/cisplatin分类
医药卫生引用本文复制引用
龚琴,王木兰,何鹿玲,冯育林,杨世林,杜力军,李俊..白头翁皂苷B4对实验性急性肾功能损伤的保护作用[J].中国现代中药,2019,21(1):62-67,70,7.基金项目
国家创新药物"十三五"重大专项(2018ZX09301030-002) （2018ZX09301030-002）
