栀子苷对大鼠的肾脏毒性作用

目的:探讨栀子苷对大鼠的肾脏毒性。方法:将大鼠随机分为空白组,栀子苷(50,100,300 mg·kg~(-1))组,每组8只。栀子苷组每日给药1次,连续给药3 d后收集大鼠尿液,分析肾脏损伤因子(KIM-1),中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平;取血液检测尿素氮(BUN)和肌酐(CRE);取肾脏组织进行肾脏病理学分析。结果:栀子苷300 mg·kg~(-1)组肾小管细胞轻度肿胀,呈现空泡样变性,显示栀子苷在该剂量下可造成肾脏毒性;50,100 mg·kg~(-1)组肾脏未见明显病理变化。栀子苷不同剂量组血液生化指标BUN,CRE无明显变化。栀子苷(300 mg·kg~(-1))组5/6大鼠的尿液KIM-1水平显著增高,3/6大鼠的尿液NGAL水平显著增高。结论:栀子苷在较高剂量(300 mg·kg~(-1))水平经口给药3 d可造成大鼠肾脏病理损伤,在该剂量下,常规用于检测肾损伤的指标血液BUN,CRE尚未产生明显变化,在常规的肾脏功能指标基础上增加尿液KIM-1检测可能更好地预测肾脏毒性。

Nephrotoxicity Effect of Gardenoside in Rats

Objective: To investigate the nephrotoxicity effect and mechanism of gardenoside in rats.Method: Rats were randomly divided into blank group, gardenoside 50 mg·kg^-1, gardenoside 100 mg·kg^-1, and gardenoside 300 mg·kg^-1 groups, n=8 in each group. The rats in gardenoside groups were given with gardenoside for 3 days, once a day. Then their urine samples were collected to analyze kidney injury molecule-1(KIM-1) and neutrophil gelatin-associated lipocalin(NGAL) levels in urine, their blood samples were taken to detect blood urea nitrogen (BUN) and creatinine (CRE) levels, their renal tissues were taken for renal pathology analysis.Result: Rats in gardenoside 300 mg·kg^-1 group showed renal toxicity. The renal tubules were slightly swelling with vacuolar degeneration. Gardenoside 50 and 100 mg·kg^-1groups showed no obvious pathological changes. There was no significant change in blood BUN and CRE levels in all gardenoside dose groups, but urine KIM-1 level was significantly increased in 5/6 rats and urine NGAL level was significantly increased in 3/6 rats of gardenoside 300 mg·kg^-1 group.Conclusion: Higher dose gardenoside (300 mg·kg^-1) could cause renal pathological injury in rats after 3 days of oral administration. Under this dose, the addition of urine KIM-1 testing based on routine renal function indexes would probably provide better prediction of nephrotoxicity.