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黄蜀葵多糖通过调节 AMPK-Sirt1-PGC-1α 信号轴介导的抗氧化作用对 2 型糖尿病模型小鼠的抗肾作用。

The anti-nephritic activity of a polysaccharide from okra (Abelmoschus esculentus (L.) Moench) via modulation of AMPK-Sirt1-PGC-1α signaling axis mediated anti-oxidative in type 2 diabetes model mice.

机构信息

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.

School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.

出版信息

Int J Biol Macromol. 2019 Nov 1;140:568-576. doi: 10.1016/j.ijbiomac.2019.08.149. Epub 2019 Aug 20.

Abstract

Diabetic nephropathy (DN) with high morbidity and mortality is one of the most severe diabetes complications and affects nearly one-third of people with diabetes. Our present experiment was designed to assess the potential therapeutic of a polysaccharide purified from okra (OP) on DN in high-fat diet-fed and streptozotocin (STZ)-induced diabetic mice. We found that an 8-week treatment with OP could significantly decrease the 24-h urine protein (24-h UP), serum creatinine (Scr), serum urea nitrogen (SUN) and glycosylated hemoglobin (HbA1c) levels, which are regard as the biomarkers of renal injury. The results of immunohistochemical analysis and histopathological examination showed that the diabetic-induced microstructural changes and fibrosis in kidney can be alleviated by the administration of OP (400 mg/kg). Our immunofluorescences results demonstrated that OP (400 mg/kg) could greatly reduce the level of reactive oxygen species (ROS) in kidney. In addition, we also studied the level of SOD, GSH, CAT, HO-1, Nrf2, p-AMPK, PGC-1α, Sirt1, Bcl-2, cleaved caspase-3 and Bax in renal tissue by assay kit and western blot. Our results suggested that OP ameliorated DN in diabetic mice, which is possibly related to suppressing apoptosis and oxidative stress through activating AMPK-Sirt1-PGC-1α signaling axis.

摘要

糖尿病肾病(DN)发病率和死亡率高,是最严重的糖尿病并发症之一,几乎影响了三分之一的糖尿病患者。我们目前的实验旨在评估从黄秋葵中纯化的多糖(OP)对高脂肪饮食喂养和链脲佐菌素(STZ)诱导的糖尿病小鼠的 DN 的潜在治疗作用。我们发现,OP 治疗 8 周可显著降低 24 小时尿蛋白(24-h UP)、血清肌酐(Scr)、血清尿素氮(SUN)和糖化血红蛋白(HbA1c)水平,这些指标被认为是肾损伤的生物标志物。免疫组织化学分析和组织病理学检查结果表明,OP(400mg/kg)可减轻糖尿病引起的肾脏微观结构改变和纤维化。我们的免疫荧光结果表明,OP(400mg/kg)可大大降低肾脏中的活性氧(ROS)水平。此外,我们还通过试剂盒和 Western blot 研究了肾脏组织中 SOD、GSH、CAT、HO-1、Nrf2、p-AMPK、PGC-1α、Sirt1、Bcl-2、cleaved caspase-3 和 Bax 的水平。我们的结果表明,OP 改善了糖尿病小鼠的 DN,这可能与通过激活 AMPK-Sirt1-PGC-1α 信号通路抑制细胞凋亡和氧化应激有关。

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