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脂联素预防高血糖状态下的肾细胞损伤。

Prevention of kidney cell damage in hyperglycaemia condition by adiponectin.

机构信息

Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran.

Department of Biology, Faculty of Science, University of Birjand, Birjand, Iran.

出版信息

Cell Biochem Funct. 2019 Apr;37(3):148-152. doi: 10.1002/cbf.3380. Epub 2019 Mar 25.

DOI:10.1002/cbf.3380
PMID:30908696
Abstract

Adiponectin (APN) is an adipocytokine, secreted from adipose tissue and has anti-inflammatory, anti-ageing, and antidiabetic properties. Hyperglycaemia can damage the renal cells, and mammalian target of rapamycin (mTOR), along with Sirtuin 1 (SIRT1), have an important role in kidney cell response to hyperglycaemia. Therefore, understanding the relationship between adiponectin, mTOR, and SIRT1 proteins is beneficial for deciphering the mechanism of adiponectin function. In this study, Human Embryonic Kidney-293 (HEK-293) cells were cultured under normal and high-glucose condition, with and without APN (1, 10, and 100 ng/mL) for 48 hours. mTOR protein expression was evaluated by western blot analysis, and SIRT1 protein was assessed using ELISA method. To evaluate hyperglycaemia-mediated cytotoxicity, cell viability was determined using MTT assay. Data showed that APN in high dose (100 ng/mL) significantly reduced the expression of mTOR and p-mTOR, increased SIRT1 protein, and also improved cell viability compared with the control high glucose (p ≤ 0.05). According to this results, APN can be useful in preventing renal cell damage, by affecting on the expression of mTOR and SIRT1 proteins, as well as increasing the survival of kidney cells in hyperglycaemia conditions. SIGNIFICANCE OF THE STUDY: Adiponectin triggered mTOR/p-mTOR/SIRT1 pathway and decreased cell death in human kidney cells. Our findings provide preliminary experimental data that support further studies on the potential therapeutic role of adiponectin in diabetes and diabetic-induced metabolic complications.

摘要

脂联素(APN)是一种脂肪细胞因子,由脂肪组织分泌,具有抗炎、抗老化和抗糖尿病的特性。高血糖可损害肾细胞,哺乳动物雷帕霉素靶蛋白(mTOR)与 Sirtuin 1(SIRT1)在肾细胞对高血糖的反应中起重要作用。因此,了解脂联素、mTOR 和 SIRT1 蛋白之间的关系有助于解析脂联素功能的机制。在本研究中,将人胚肾-293(HEK-293)细胞在正常和高葡萄糖条件下培养,分别加入和不加入脂联素(1、10 和 100ng/mL)48 小时。通过 Western blot 分析评估 mTOR 蛋白的表达,通过 ELISA 法评估 SIRT1 蛋白。为评估高血糖介导的细胞毒性,通过 MTT 测定法确定细胞活力。结果显示,高剂量脂联素(100ng/mL)与高葡萄糖对照相比,显著降低了 mTOR 和 p-mTOR 的表达,增加了 SIRT1 蛋白,并提高了细胞活力(p≤0.05)。根据这些结果,脂联素可通过影响 mTOR 和 SIRT1 蛋白的表达以及增加高血糖条件下肾细胞的存活,从而有助于预防肾细胞损伤。研究意义:脂联素触发 mTOR/p-mTOR/SIRT1 通路并减少人肾细胞的死亡。我们的研究结果提供了初步的实验数据,支持进一步研究脂联素在糖尿病和糖尿病诱导的代谢并发症中的潜在治疗作用。

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