Abstract：
BACKGROUND: Autophagy is a well-preserved mechanism essential in minimizing endoplasmic reticulum stress (ER)-related cell death. Defects in β-cell autophagy have been linked to type 1 diabetes, particularly deficits in the secretion of insulin, boosting ER stress sensitivity and possibly promoting pancreatic β-cell death. Quercetin (QU) is a potent antioxidant and anti-diabetic flavonoid with low bioavailability, and the precise mechanism of its anti-diabetic activity is still unknown. Aim This study aimed to design an improved bioavailable form of QU (liposomes) and examine the impact of its treatment on the alleviation of type 1 diabetes induced by STZ in rats.
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.
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.
摘要：
背景：自噬是一种保存完好的机制，可将内质网应激（ER）相关的细胞死亡降至最低。β细胞自噬缺陷与1型糖尿病有关,特别是胰岛素分泌不足，提高内质网应激敏感性并可能促进胰腺β细胞死亡。槲皮素（QU）是一种有效的抗氧化剂和抗糖尿病类黄酮，生物利用度低，其抗糖尿病活性的确切机制仍然未知。目的本研究旨在设计一种改进的QU（脂质体）生物可利用形式，并研究其治疗对减轻STZ诱导的大鼠1型糖尿病的影响。
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。
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。
