毒理学杂志

目的研究不同剂量替考拉宁(TEC)对大鼠的急性肾损伤程度及肾损伤与氧化应激的关系。方法 SD大鼠32只随机分为4组(n=8),TEC 100、200和400 mg/kg组和对照组,TEC 100、200和400 mg/kg组分别日腹腔注射100、200和400 mg/kg·bw的TEC,对照组每日腹腔注射生理盐水,连续7 d。用化学发光法检测血清尿素氮(BUN)及肌酐(Scr)水平,比色法测定肾脏组织中谷胱甘肽(GSH)及硫代巴比妥酸法测定丙二醛(MDA)浓度,黄嘌呤氧化酶法检测超氧化物歧化酶(SOD)活性,苏木素-伊红(HE)染色观察肾组织病理学变化,免疫组化分析核因子E2相关因子(Nrf2)的表达情况。结果与对照组相比较,TEC 400 mg/kg组大鼠血浆BUN、Scr浓度明显升高(P<0.01),肾组织GSH、MDA浓度明显升高(P<0.01),SOD活性明显降低(P<0.01),肾组织Nrf2表达上调。结论 TEC可诱导大鼠急性肾功能损伤,且可能是通过氧化应激途径所导致。

Objective Research about kidney injury and oxidative stress by different dose of teicoplanin(TEC) in rats. Methods Thirty two rats were randomly separated into four groups(n=8). TEC 100,200,400 mg/kg groups and blank group, TEC 100,200,400 mg/kg groups were given teicoplanin 100, 200,400 mg/kg·bw through intraperitoneal injection once a day, blank group was given normal saline through intraperitoneal injection once a day. Serum concentrations of Scr and Bun were detected using chemiluminescence technique. The levels of GSH, MDA and SOD in renal homogenate were detected using colorimetry, thiobarbituric acid and xanthine oxidase method. The histological changes of the renal were observed via HE staining, and the protein levels of Nrf2 in the renal tissue was determined by immunohistochemistry. Result Compared with blank group, the levels of Scr and Bun in serum in TEC 400 mg/kg group was increased significantly(P<0.01).The levels of GSH and MDA in renal homogenate were increased significantly(P<0.01), the activity of SOD was decreased significantly(P<0.05). The expression of Nrf2 was up-regulated. Conclusion It was suggested that TEC could induce renal injury and the primary mechanism may be related with the oxidative stress.