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目的研究内源性物质3-硫酸吲哚酚用于肾损伤早期诊断的意义。方法以抗癌药顺铂、甲氨蝶呤为研究对象,取雄性Sprague-Dawley大鼠36只,随机分为3组,分别为顺铂组、甲氨蝶呤组和空白组。于给药后第1、3和5天采集血清与新鲜肾组织。采用LC-MS法测定各组大鼠血清中3-硫酸吲哚酚的质量浓度;同时分析各组大鼠血清中生化指标肌酐和尿素氮浓度以及肾脏组织病理学变化。结果单次给药后,肾组织病理学结果显示顺铂组与甲氨蝶呤组大鼠在第3天均可见明显肾损伤;各组中内源性物质3-硫酸吲哚酚于第3天明显升高;顺铂组肌酐与尿素氮于第5天明显升高,甲氨蝶呤组肌酐与尿素氮无明显变化。结论在顺铂和甲氨蝶呤致肾损伤模型中,内源性物质3-硫酸吲哚酚显示了较常规生化指标血肌酐与尿素氮更高的灵敏度。
Objective To study the significance of the endogenous substance 3-indoxyl sulfate in the early diagnosis of renal injury. Methods Thirty six male Sprague-Dawley rats were randomly divided into three groups: cisplatin group, methotrexate group and blank group. Serum and fresh kidney tissue were harvested on days 1, 3 and 5 after dosing. The concentration of indoxyl 3-sulfate was determined by LC-MS. Serum biochemical markers of creatinine and urea nitrogen and pathological changes of kidney were also analyzed. Results After a single administration, the renal histopathological results showed that both the cisplatin group and the methotrexate group showed obvious renal injury on the 3rd day. In each group, the endogenous substance 3-indoxyl sulfate was found on the 3rd Day significantly increased; creatinine and urea nitrogen in cisplatin group was significantly increased on the 5th day, creatinine and urea nitrogen in methotrexate group had no significant change. Conclusions In the model of renal injury induced by cisplatin and methotrexate, the endogenous substance 3-indoxyl sulfate shows a higher sensitivity than the conventional biochemical markers of serum creatinine and urea nitrogen.