栀子苷对正常大鼠急性肝、肾毒性的时-毒关系分析

目的:考察栀子苷对正常大鼠急性肝、肾毒性的时-毒关系,为栀子临床安全应用提供科学依据。方法:Wistar大鼠110只,随机分为正常组,给药后不同时间组(0.5,1,2,4,8,12,24,48,72 h组),除正常组灌服生理盐水外,其余组按剂量1.2 g·kg-1灌服栀子苷。按组在灌胃后相应时间眼眶静脉取血,离心取血清,检测血清天门冬氨酸氨基转移酶(AST),碱性磷酸酶(ALP),丙氨酸氨基转移酶(ALT),总胆红素(TBIL),尿素氮(BUN),肌酐(Cr)活性,观察肝肾毒性损伤情况。结果:与正常组比较,在给药12 h后AST,ALP,ALT,TBIL,BUN,Cr明显升高(P0.05,P0.01),在给药24,48 h后AST,ALP,ALT,TBIL,BUN,Cr出现峰值,72 h后明显下降,240 h可见基本恢复正常。病理组织学检查出现不同程度的汇管区炎细胞浸润、肝细胞坏死、汇管区胆管轻度增生、纤维组织增生等病理变化。结论:栀子苷(1.2 g·kg-1)对正常大鼠存在急性肝、肾毒性且存在一定的时-毒关系。

Time-toxicity Relationship of Geniposide on Hepatotoxicity and Nephrotoxicity in Normal Rats

Objective: To observe the time-toxicity relationship of geniposide on hepatotoxicity and nephrotoxicity in normal rats, and provide scientific basis for the clinical application of gardenia. Method: The 110 Wistar rats were randomly divided into normal group, different time groups(0.5, 1, 2, 4, 8, 12, 24, 48, 72 h group). The rats in normal group received normal saline by gavage, and the rats in other groups received 1.2 g·kg^-1 geniposide by gavage. Orbital venous blood was taken at corresponding time points after gavage, and the serum was taken by centrifugation. aspartate amino transferase(AST), alkaline phosphatase(ALP), alkaline phosphatase(ALT), total bilirubin(TBIL), urea nitrogen(BUN), and creatinine(Cr) activities in serum were detected to indicate the toxicity of kidney and liver injury. Result: 12 h after administration of geniposide, AST, ALP,ALT, TBIL, BUN, and Cr levels were significantly higher than those in normal group(P<0.05,P<0.01). 24 h and 48 h after administration of geniposide, AST, ALP, ALT, TBIL, BUN, and Cr levels came to peak values. 72 h after administration of geniposide, AST, ALP, ALT, TBIL, BUN, and Cr levels began to significantly decrease. 240 h after administration, the values basically returned to normal levels. In histopathologic examination, different degree''s infiltration of inflammatory cells in portal area, necrosis of liver cells, mild hyperplasia of bile duct in portal area, proliferation of fibrous tissue and other pathological changes were observe. Conclusion: Geniposide at dose of 1.2 g·kg^-1 can cause acute liver and kidney injury on rats and show certain time-toxicity relationship.