普罗布考对多柔比星肾病大鼠的保护作用及其机制研究

Study of Protective Effect and Mechanism of Probucol in Rats with Doxorubicin-induced Nephropathy

目的:观察普罗布考对多柔比星肾病大鼠肾脏的保护作用并探讨其作用机制。方法:40只雄性SD大鼠随机分为对照组、模型组、治疗组。尾静脉一次性注射多柔比星6mg·kg^(-1)制备多柔比星肾病模型。1周后开始药物干预,模型组每天温开水灌胃,治疗组每天500mg·kg^(-1)·d^(-1)普罗布考灌胃,持续4周。4周后检测大鼠24h尿蛋白定量、血清总胆固醇(TC)、三酰甘油(TG)、尿素氮(BUN)、血清肌酐(Scr)、血清及肾组织SOD活性和MDA含量,同时取肾组织标本观察病理学改变。结果:与模型组相比,治疗组24h尿蛋白排泄量和血脂明显下降(P<0.05),肾指数明显改善(P<0.05),血清和肾组织中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:普罗布考能提高多柔比星肾病大鼠血和肾组织中SOD活性,降低血脂,减少蛋白尿,减轻肾组织的病理改变,具有肾保护作用。

Objective： To investigate the protective effects of probucol in rats with doxorubicin-induced nephropathy, and explore its protective mechanims. Method： Forty male SD rats were randomly divided into three groups, namely normal group （A）, model group （B） and treated group （C）. The models of doxorubicin-induced nephropathy were established by tail vein injection of 6 mg·kg^-1doxorubicin. After 1 week,B group was given warm water and C group was fed with probucol（500 mg·kg^-1 ·d^-1） by garage for 4 weeks. The levels of 24-hour urinary protein and blood biochemistry indices were measured, and renal pathological changes were examined. Result： In the treated group,24-hour urinary protein and blood fat levels were significantly decreased （P 〈 0. 05 ） with improved renal index. The SOD activity was significantly increased and MDA wase significantly decreased （P 〈 0. 05 ） with alleviated renal pathological damage. Conclusion： In rats with doxorubicin-induced nephropathy, probucol can improve the SOD activity, decrease the blood fat levels and the urinary protein and improve the renal pathological changes with renoprotective effect.