Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Biomed Pharmacother. 2017 Aug;92:331-339. doi: 10.1016/j.biopha.2017.05.086. Epub 2017 May 26.
The development of complementary treatment strategies that focuses on achieving a balance between adaptive and apoptotic unfolded protein response (UPR), enhancing endoplasmic reticulum (ER) homeostasis, and thus preserving β cell mass and function is particularly warranted.
This study was designed to investigate the effectiveness of the combined treatment by Quercetin (QUE) and Liraglutide (LIRA) in modulating hyperglycemia, insulin-insensitivity, UPR/ER stress markers, apoptosis, oxidative stress and inflammation using a high-fat diet/streptozotocin -induced type 2 diabetic rat model.
Sixty male albino rats were allocated into five equal groups: normal control, diabetic control, LIRA treated diabetic; QUE treated diabetic and combined treatment diabetic groups. Fasting glucose, insulin, CHOP, macrophage inflammatory protein -1 α (MIP-1α) and Bax, Bcl levels were estimated by ELISA; mRNA expression levels of the spliced X-box binding protein 1 (XBP1) were estimated using quantitative real-time RT-PCR, while MDA, advanced oxidation protein products, reduced glutathione levels and protein disulfide isomerase (PDI) activity were evaluated spectrophotometrically. Pancreatic tissues were also subjected to histopathological examination.
The combined treatment with both LIRA and QUE causes significant improvements in all the studied parameters; including XBP1 splicing, CHOP, MIP-1α, Bax/Bcl ratio, PDI activity, as well as oxidative stress markers as compared to either treatment alone. It also attenuated pancreatic histopathological damage.
Our study nominates this combination to be used in T2DM to achieve adequate glycaemic control and to preserve optimal β cell function.
特别需要开发一种互补的治疗策略，该策略侧重于在适应性和凋亡未折叠蛋白反应（UPR）之间实现平衡，增强内质网（ER）的稳定性，从而维持β细胞的质量和功能。
本研究旨在通过使用高脂肪饮食/链脲佐菌素诱导的 2 型糖尿病大鼠模型，研究槲皮素（QUE）和利拉鲁肽（LIRA）联合治疗在调节高血糖、胰岛素不敏感、UPR/ER 应激标志物、细胞凋亡、氧化应激和炎症方面的有效性。
将 60 只雄性白化大鼠分配到 5 个相等的组中：正常对照组、糖尿病对照组、LIRA 治疗的糖尿病组、QUE 治疗的糖尿病组和联合治疗的糖尿病组。通过 ELISA 测定空腹血糖、胰岛素、CHOP、巨噬细胞炎性蛋白-1α（MIP-1α）和 Bax、Bcl 水平；通过定量实时 RT-PCR 测定剪接 X 盒结合蛋白 1（XBP1）的 mRNA 表达水平，同时通过分光光度法评估 MDA、高级氧化蛋白产物、还原型谷胱甘肽水平和蛋白二硫键异构酶（PDI）活性。还对胰腺组织进行了组织病理学检查。
与单独治疗相比，LIRA 和 QUE 的联合治疗可显著改善所有研究参数，包括 XBP1 剪接、CHOP、MIP-1α、Bax/Bcl 比值、PDI 活性以及氧化应激标志物。它还减轻了胰腺组织病理学损伤。
我们的研究提名这种联合治疗用于 2 型糖尿病，以实现适当的血糖控制并保持最佳的β细胞功能。
