罗格列酮对多柔比星所致肾病大鼠的保护作用及其抗氧化机制研究

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目的:研究罗格列酮对多柔比星所致肾脏氧化应激损伤大鼠肾脏的保护作用并探讨其作用机制。方法:采用MTT法测定不同浓度的罗格列酮对多柔比星作用下细胞的增殖活性的影响。50只雄性SD大鼠随机分为空白对照组、多柔比星对照组和罗格列酮治疗组,大鼠尾静脉一次性注射多柔比星6.5 mg.kg-1制备多柔比星肾病模型。1周后,空白对照组每天蒸馏水灌胃,治疗组每天分别灌胃给予20、10和5mg.kg-1罗格列酮,持续8周。8周后检测大鼠血清尿素氮(BUN)和肌酐(Scr)水平及肾组织各氧化指标,同时取肾组织标本观察病理学改变。结果:用罗格列酮孵育能够明显提高DOX作用下HEK29细胞存活率;与模型对照组相比,罗格列酮20 mg.kg-1组血清肌酐、尿素氮明显下降(P<0.05),肾组织中NO含量、NOS和SOD活性明显上升、MDA含量明显下降(P<0.05),肾组织病理损伤减轻。结论:罗格列酮能降低多柔比星所致大鼠肾脏氧化应激损伤,具有肾保护作用。 Objective: To study the protective effect of rosiglitazone on the kidney of oxidative stress injury induced by doxorubicin in rats and its mechanism. Methods: MTT assay was used to determine the effect of different concentrations of rosiglitazone on the proliferation of cells under the action of doxorubicin. 50 male Sprague-Dawley rats were randomly divided into blank control group, doxorubicin control group and rosiglitazone treatment group, a single injection of doxorubicin 6.5 mg.kg-1 into the tail vein of rats to prepare doxorubicin nephropathy model. One week later, the blank control group was orally administered with distilled water every day, and the treatment group was orally administered with 20, 10 and 5 mg.kg-1 rosiglitazone daily for 8 weeks. After 8 weeks, the levels of serum urea nitrogen (BUN) and creatinine (Scr) and the indexes of renal tissue oxidation were detected. At the same time, the pathological changes of kidney were observed. RESULTS: Incubation with rosiglitazone significantly increased the survival rate of HEK29 cells treated with DOX. Serum creatinine and urea nitrogen were significantly decreased in rosiglitazone 20 mg.kg-1 group compared with model control group (P <0.05) The content of NO, the activity of NOS and SOD in kidney increased obviously, the content of MDA decreased obviously (P <0.05), and the pathological damage of renal tissue was alleviated. CONCLUSION: Rosiglitazone can reduce the oxidative stress injury induced by doxorubicin in the kidneys of rats and has a protective effect on kidney.
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