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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 investigate the effect and mechanism of rosiglitazone on early diabetic nephropathy in diabetic rats. Methods: Streptozotocin (STZ) -induced diabetic rat model was used as the research object. Rosiglitazone 5 mg · kg -1 and 20 mg · kg -1 were given daily for 4 weeks. The blood glucose (BS), blood lipid and 24h urinary albumin level were detected in each group. The rats were then sacrificed and the contents of MDA, T-AOC, Cu-ZnSOD, GSH- Px), transcription activator protein-1 (AP-1) activity. At the same time, renal tissue was collected for PAS staining for pathological examination. The contents of TGF-β 1 mRNA and protein in renal tissues were detected by reverse transcription-polymerase chain reaction (PT-PCR) and immunohistochemistry respectively. Results: Compared with the diabetic group, the levels of serum lipid and BS, serum lipids did not change significantly in the intervention group of rosiglitazone 20 mg · kg -1, but the contents of MDA and TGF-β 1 mRNA and protein in the kidney decreased significantly Lower, but no significant difference. The antioxidant enzyme activity of kidney, including SOD, GSH-Px, T-AOC was significantly increased. Pathological examination found that the group than the diabetic group glomerular area, the volume decreases. Conclusion: Rosiglitazone can significantly improve the early kidney damage in diabetic rats. Mechanism may be related to its antioxidant, down-regulated TGF-β1 expression.