METHODS: Seventy SD rats were allocated into seven equal groups 10 rats of each: control, STZ, STZ + 3-MA, STZ + QU-Lip, and STZ + 3-MA + QU-Lip. Fasting blood glucose, insulin, c-peptide, serum IL-6, TNF-α, pancreatic oxidative stress, TRAF-6, autophagy, endoplasmic reticulum stress (ER stress) markers expression and their regulatory microRNA (miRNA) were performed. As well as, docking analysis for the quercetin, ER stress, and autophagy were done. Finally, the histopathological and immunohistochemical analysis were conducted.
CONCLUSIONS: QU-Lip significantly decreased glucose levels, oxidative, and inflammatory markers in the pancreas. It also significantly downregulated the expression of ER stress and upregulated autophagic-related markers. Furthermore, QU-Lip significantly ameliorated the expression of several MicroRNAs, which both control autophagy and ER stress signaling pathways. However, the improvement of STZ-diabetic rats was abolished upon combination with an autophagy inhibitor (3-MA). The findings suggest that QU-Lip has therapeutic promise in treating type 1 diabetes by modulating ER stress and autophagy via an epigenetic mechanism.
方法:将70只SD大鼠分为7组,每组10只:对照组,STZ,STZ+3-MA,STZ+QU-Lip,和STZ+3-MA+QU-Lip。空腹血糖,胰岛素,c-肽,血清IL-6,TNF-α,胰腺氧化应激,TRAF-6,自噬,内质网应激(ER应激)标记物表达及其调节microRNA(miRNA)。还有,槲皮素的对接分析,ER压力,自噬完成了。最后,进行组织病理学和免疫组织化学分析。
结论:QU-Lip显著降低血糖水平,氧化,和胰腺中的炎症标记物。它还显着下调ER应激的表达并上调自噬相关标志物。此外,QU-Lip显着改善了几种MicroRNAs的表达,它们都控制自噬和ER应激信号通路。然而,与自噬抑制剂(3-MA)联用后,STZ-糖尿病大鼠的改善作用被消除.研究结果表明,QU-Lip通过表观遗传机制调节内质网应激和自噬,在治疗1型糖尿病方面具有治疗前景。