槲皮素通过调节肾脏na +、k + - atp酶表达和氧化应激改善大鼠糖尿病肾病

S. Bashir, M. D. Morsy, H. Sakr, H. Refaey, R. Eid, M. Alkhateeb, Moataz A. Defallah
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引用次数: 16

摘要

糖尿病肾病(Diabetic Nephropathy, DN)是糖尿病(Diabetes Mellitus, DM)最常见的并发症之一,其防治是一个重要的研究领域。槲皮素是一种植物类黄酮,具有降血糖和抗氧化的特性,被认为对糖尿病有保护肾的作用。本研究旨在探讨槲皮素治疗对糖尿病大鼠的生化和病理变化的预防作用,并确定其作用是否通过调节氧化应激和Na +、K + atp酶的表达和活性来介导。雄性sd - dawley大鼠60只,平均分为6组:(i)对照组(C), (ii)槲皮素治疗对照组(CQ), (iii)糖尿病组(D), (iv)糖尿病胰岛素治疗组(DI), (v)糖尿病槲皮素治疗组(DQ)和(vi)糖尿病胰岛素和槲皮素治疗组(DIQ)。实验结束时(8周)测量收缩压。眼眶后血样本用于测定血清葡萄糖、糖化血红蛋白、尿素、肌酐、Na +和K +水平。测定肾脏匀浆中Na +、K + atp酶活性、丙二醛(MDA0)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)水平。进行半定量逆转录- pcr检测Na +、K + atp酶表达及肾脏组织病理学检查。单独使用胰岛素或槲皮素治疗可部分逆转糖尿病大鼠肾病的生化和组织病理学征象。这与氧化应激指标和Na +、K + atp酶基因表达和活性的部分但显著改善有关。然而,只有胰岛素和槲皮素联合治疗才能显著改善上述所有参数,达到对照水平。这些结果提示胰岛素和槲皮素联合治疗可能是预防DN发展的有效工具。
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QUERCETIN AMELIORATES DIABETIC NEPHROPATHY IN RATS VIA MODULATION OF RENAL NA + , K + -ATPASE EXPRESSION AND OXIDATIVE STRESS
Diabetic Nephropathy (DN) is one of most prevalent complications of Diabetes Mellitus (DM), therefore prevention of its development is a important field for researches. Quercetin is a plant flavenoid with hypoglycemic and antioxidant properties that is cla imed to have a reno-protective effect in diabetes. This study was designed to investigate the reno-preventi ve role of Quercetin treatment in terms of biochemi cal and pathological changes in diabetic rats and to de termine whether the effect is mediated through modulation of oxidative stress and Na + , K + ATPase expression and activity. Sixty male Sprague-Dawley rats were distributed equally among 6 groups: (i) Contro l group (C), (ii) Quercetin treated Control group ( CQ), (iii) Diabetic group (D), (iv) Diabetic Insulin tre ated group (DI), (v) Diabetic Quercetin treated gro up (DQ) and (vi) Diabetic Insulin and Quercetin treated gro up (DIQ). Systolic blood pressure was measured at t he end of the experiments (8 weeks). Retro-orbital blo od samples were used to determine the serum levels of glucose, HbA1c, urea, creatinine, Na + and K + . Renal homogenate levels of Na + , K + ATPase activity, Malondialdehyde (MDA0, Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) were measured. Semiquantitative reverse transcriptase-PCR Na + , K + ATPase expression assays and kidney histopathological examination were conducted. Treatment with either insulin or Quercetin alone resulted in partial rever sal of the biochemical and histopathological signs of neph ropathy in diabetic rats. This was associated with partial but significant amelioration of indicators of oxida tive stress and Na + , K + ATPase gene expression and activity. However only combined treatment by both insulin and Quercetin significantly improved all of the aforementioned parameters up to the control levels. These results suggested that combined therapy with insulin and Quercetin might be a useful preventive tool aga inst development of DN.
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