Keyhanmanesh Rana, Hamidian Gholamreza, Lotfi Hajie, Zavari Zohre, Seyfollahzadeh Monireh, Ghadiri Afsane, Ahmadi Mehdi, Bahari Farzad, Mirzaei Bavil Fariba
Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Emergency Medicine Research Group, Tabriz University of medical sciences, Tabriz, Iran.
Avicenna J Phytomed. 2022 Mar-Apr;12(2):109-115. doi: 10.22038/AJP.2021.18875.
Nephropathy is known to be the leading cause of kidney failure in diabetic patients. Troxerutin, as a flavonoid component, could provide a novel protective strategy in the prevention of diabetic nephropathy. A large number of reports on the salutary effects of troxerutin inspired us to investigate its effect on the nephropathy signaling events (i.e., expression of TGF-β, miRNA192, and SIP1) in type-1 induced diabetic rats.
50 male Wistar rats were divided into 5 groups including control group, sham group treated with troxerutin for 4 weeks, diabetic group induced by streptozotocin (STZ) injection, DI group including insulin-treated diabetic animals and DT group treated with troxerutin. Ultimately, rat kidneys were extracted, and the level of miR-192 (using qPCR), transforming growth factor-beta (TGF-β), and smad interacting protein 1 (SIP1) using an ELISA kit, was measured.
The level of TGF-β and miRNA192 significantly increased in the diabetic group. However, their expression levels decreased following the administration of troxerutin and insulin (p<0.05) compared to control group. SIP1 was down-regulated in the diabetic group, whereas a spike in the expression levels was observed after troxerutin administration compared to control and troxerutin groups (p<0.05). However, no significant difference was found in the effects of insulin and troxerutin on the level of miR-192, SIP1, and TGF- β.
According to the previous literatures, during the progression of nephropathy, TGF-β represses SIP1 (the repression region in the collagen gene) by increasing the expression of miR-192. Ultimately, in this study, diabetes led to up-regulation of TGF-β while troxerutin proved to have a protective effect on the kidney by increasing SIP and lowering miR-192 levels.
已知肾病是糖尿病患者肾衰竭的主要原因。曲克芦丁作为一种黄酮类成分，可为预防糖尿病肾病提供一种新的保护策略。大量关于曲克芦丁有益作用的报道促使我们研究其对1型诱导糖尿病大鼠肾病信号事件（即转化生长因子-β（TGF-β）、微小RNA192（miRNA192）和Smad相互作用蛋白1（SIP1）的表达）的影响。
将50只雄性Wistar大鼠分为5组，包括对照组、用曲克芦丁治疗4周的假手术组、通过注射链脲佐菌素（STZ）诱导的糖尿病组、包括胰岛素治疗的糖尿病动物的DI组和用曲克芦丁治疗的DT组。最终，提取大鼠肾脏，使用定量聚合酶链反应（qPCR）检测miR-192水平，使用酶联免疫吸附测定（ELISA）试剂盒检测转化生长因子-β（TGF-β）和Smad相互作用蛋白1（SIP1）水平。
糖尿病组中TGF-β和miRNA192水平显著升高。然而，与对照组相比，给予曲克芦丁和胰岛素后，它们的表达水平降低（p<0.05）。糖尿病组中SIP1表达下调，而与对照组和曲克芦丁组相比，给予曲克芦丁后观察到其表达水平升高（p<0.05）。然而，胰岛素和曲克芦丁对miR-192、SIP1和TGF-β水平的影响未发现显著差异。
根据以往文献，在肾病进展过程中，TGF-β通过增加miR-192的表达来抑制SIP1（胶原基因中的抑制区域）。最终，在本研究中，糖尿病导致TGF-β上调，而曲克芦丁通过增加SIP并降低miR-192水平对肾脏具有保护作用。
