| 白头翁皂苷B4对实验性急性肾功能损伤的保护作用 |
| 投稿时间：2018-08-20 点此下载全文
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| 引用本文：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 |
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| 基金项目:国家创新药物“十三五”重大专项（2018ZX09301030-002） |
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| 中文摘要:目的：研究探讨白头翁皂苷B4对急性肾功能损伤的保护作用，以及对其进行小鼠急性毒性评价。方法：通过体外细胞实验，以LPS诱导人胚肾细胞HEK293损伤模型，用白头翁皂苷B4进行干预24、48 h，MTT法检测细胞活性及炎性因子的表达，观察白头翁皂苷B4对肾细胞损伤的作用。整体动物实验，分别以甘油、顺铂和脂多糖（LPS）造成大鼠或小鼠急性肾功能损伤，尾静脉注射不同剂量的白头翁皂苷B4，给药一定时间后行眼眶采血，分离血清，检测反映肾功能指标的尿素氮（BUN）、肌酐（Cre）、总蛋白（TP）及尿液中蛋白含量，来观察白头翁皂苷B4对急性肾功能损伤的作用；给小鼠尾静脉注射不同剂量的白头翁皂苷B4，连续观察2周，根据死亡率计算半数致死量（LD50），初步评价白头翁皂苷B4的用药安全性。结果：白头翁皂苷B4能提高损伤的肾细胞活性，下调炎性因子TNF-α的表达。白头翁皂苷B4静脉给药对甘油，顺铂和LPS所导致的血清BUN，Cre升高均有明显的抑制作用，同时白头翁皂苷B4高剂量（2.5 mg·kg-1）还可以明显降低甘油致急性肾损伤大鼠的尿蛋白浓度，其在大鼠有效剂量为1.25～2.5 mg·kg-1，小鼠有效剂量为5～10 mg·kg-1。白头翁皂苷B4对小鼠静脉给药的LD50为3.36 g·kg-1，95%可信限为3.34～3.37 g·kg-1，根据小鼠最大给药剂量20 mg·kg-1，计算出其临床安全指数为168（3.36/0.02），具有较高的临床安全范围。结论：白头翁皂苷B4对于实验性急性动物肾功能损伤具有明确的保护作用，同时以其较大的临床安全指数提示该化合物具有较好的新药开发前景。 |
| 中文关键词: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 |
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| Protective Effect of Anemoside B4 from Experimental Acute Renal Damage in Animal |
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| 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 qPCR 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 for 2 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-1 in rats，and 5-10 mg·kg-1 in mice.The LD50 for intravenous administration of B4 to mice was 3.36 g·kg-1 and 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-1 in 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. |
| keywords:nemoside B4 renal damage acute toxicity human embryonic kidney cells HEK293 LPS glycerin cisplatin |
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