摘要
目的:探讨罗格列酮对糖尿病大鼠早期肾脏病变的改善作用及其机制。方法:采用链脲菌素(STZ)诱导的糖尿病大鼠模型作为研究对象。每日给予罗格列酮5mg·kg^(-1)、20 mg·kg^(-1)灌胃,共4周。检测各组大鼠的血糖(BS)、血脂及24h尿白蛋白水平。随后处死大鼠,测定肾组织中丙二醛(MDA)含量、总抗氧化能力(T-AOC)及铜锌超氧化物歧化酶(Cu-ZnSOD)、谷胱甘肽过氧化酶(GSH-Px)、转录激活蛋白-1(AP-1)的活性。同时留取肾脏组织作PAS染色进行病理检查。分别用逆转录-聚合酶链式反应(PT-PCR)和免疫组化法检测肾组织中转化生长因子-β_1(TGF-β_1)mRNA及蛋白质的含量。结果:与糖尿病组相比,罗格列酮20mg·kg^(-1)干预组BS、血脂水平无明显变化,但肾脏MDA、TGF-β_1mRNA及蛋白质含量明显下降,AP-1活性虽有所降低,但没有显著性差异。而肾脏抗氧化酶活性,包括SOD、GSH-Px、T-AOC则明显上升。病理检查发现该组较糖尿病组肾小球面积、体积减小。结论:罗格列酮可明显改善糖尿病大鼠的早期肾脏损害。机制可能与其抗氧化,下调TGF-β1的表达有关。
Objective ： To study renal protection of rosiglitazone on diabetic rats. Method ： Diabetic rats were induced by streptozotocin, and rosiglitazone （5 or 20 mg. kg^- 1 ） was orally administered once a day for 4 weeks. Blood glucose,lipid and 24h urinary albumin were measured. MDA（ lipid peroxidatin）, the activities of activating protein-1 （AP-1） and antioxidant enzymes including Cu-Zn superoxide dismutase （Cu-Zn SOD）, glutathione peroxidase （GSH-Px） and total antioxidative capacity （T-AOC） in kidney were exam- ined too. Immunohistochemistry and reverse transcripition-polymerase chain reaction （RT-PCR） were used to determined the expression of TGF-β1 in renal tissue. Result： Elevated content of 24h urinary albumin , MDA and TGF-β1 in diabetic rats were significantly attenuated by treatment with high dose rosiglitazone, though rosiglitazone did not affect the level of blood glucose and lipid. The decreased activities of Cu-Zn SOD, GSH-Px, T-AOC in renal tissue of diabetic rats were improved by high dose rosiglitazone. Rosiglita- zone can slightly degrade the activities of AP-1 in diabetic rats, but there were no significance. Conclusion： Rosiglitazone may play a protective role of the kidney by lightening oxidative stress, and down-regulating TGF-β1 in diabetic rats.
出处
《中国药师》
CAS
2009年第12期1698-1701,共4页
China Pharmacist
