摘要目的 探讨罗格列酮对衰老大鼠.肾脏抗氧化能力的影响.方法 24月龄SD雄性大鼠30只,按数字随机法分成3组,每组10只:对照组(CON组)为自由摄食;罗格列酮组(RGTZ组)为自由摄食,并以罗格列酮4 mg·kg-1·d-1灌胃;限制饮食组(CR组)能量摄入为CON组的60%.干预12周后断头处夕匕所有动物,对比各组大鼠干预前后的体质量变化;观察干预后各组大鼠的肾质量及心质最与体质量之比;Western印迹分析肾组织内过氧化物酶体增殖物激活受体γ(PPARγ)蛋白表达;检测肾组织匀浆超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活力及丙二醛(MDA)的含量;肾组织冰冻切片行β半乳糖苷酶(β-Ga1)染色.结果 干预后CR组大鼠体质量明显下降(P<0.05),而CON组及RGTZ组无显著变化.各组大鼠干预前后肾质量与体质量比、心质量与体质量比均无显著,变化.PPARγ蛋白表达在RGTZ组与CR组显著上调(P<0.01,P<0.05).CR组及RGTZ组肾组织SOD、GSH-PX酶活力均显著高于CONT组(P<0.01),MDA的含量均显著低于CON组(P<0.01,P<0.05).RGTZ组、CR组β-Gal染色阳件面积明显低于CON组(P<0.05,P<0.01).结论 罗格列酬能够减轻衰老大鼠肾组织的氧化损伤、增强其抗氧化能力,从而起到延缓大鼠肾脏衰老的作用.
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abstractsObjective To investigate the effect of rosiglitazone (RGTZ) on anti-oxidation in aging rat kidney. Methods Twenty-four-month-old male Sprague-Dawley rats were randomly divided into three groups (n=10): control group (CON), rosiglitazone group (RGTZ) and caloric restriction group (CR). The CON rats were allowed ad libitum access to feed and tap water.The RGTZ rats received intragastric administration of RGTZ (4 mg·kg-1·d-1),and the CR rats were provided with a vitamin and mineral fortified version of the same diet at a level of 40% less food (by weight) than the CON rats. After 12 weeks all the animals were sacrificed by decapitation, and both the body weight and the percentage of kidney and heart in each group were measured.Western blot was performed to analyze the expression of PPARγ protein. The content of MDA and the activity of SOD and GSH-PX in kidney tissue were detected. Besides, frozen sections of kidney tissue were stained for senescence-associated-13 galactosidase (SA-β-Gal). Results The body weight of CR rats decreased obviously, in contrast, which did not change in CON and RGTZ group. Percentage of kidney and heart to body weight was normal in CR or RGTZ group after intervention. Western blot result showed that PPARγ protein expression in rat kidney was significantly higher in RGTZ and CR group as compared to CON group (P<0.05). Compared with RGTZ and CR rats, obviously lower activities of SOD and GSH-Px were noted in CON rats, however, the content of MDA was higher in CON rats. Additionally, the positive staining area of [3-Gal in CR and RGTZ group was significantly smaller than that in CON rats (P<0.05, P<0.01 ). Conclusion RGTZ can defer the kidney aging in senescence SD rat, and the mechanism may be related to amelioration of oxidative damage and enhancement of antioxidation.
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