Testicular damage and testosterone secretion disorder are associated with diabetes mellitus. Quercetin, a common flavonoid, has antioxidant, anti-cancer, and blood sugar lowering effects. Therefore, this study aims to investigate the effect of quercetin on the reproductive system of male rats with diabetes in vivo and in vitro and elucidate its mechanism. Streptozotocin (STZ) induction was used to establish a diabetes model in forty male Sprague Dawley (SD) rats, which were subsequently administered with 20 or 50 mg/kg of quercetin. Leydig cells of rat testes were treated by high glucose (HG) followed by 5 or 10 μM quercetin. Two doses of quercetin increased rat body weight and testicular weight, decreased blood glucose,and inhibited oxidative stress. RT-qPCR and Western blotting revealed that quercetin alleviated STZ-induced testicular damage and promoted testosterone synthesis. Both doses of quercetin reduced ROS and MDA levels, and increased SOD level in HG-treated cells. Both, in vivo and in vitro results confirmed that a high dose of quercetin was more effective. MiR-1306-5p was upregulated in testicular tissue of diabetic rats and HG-treated cells. 17β-hydroxysteroid dehydrogenase (HSD17B7) was a target of miR-1306-5p and HSD17B7 was downregulated in STZ-induced rat tissues and HG-treated cells. HSD17B7 overexpression reversed the increase of C/EBP homologous protein (CHOP) and glucose-regulated protein 78 (Grp78) protein levels as well as eIF2α phosphorylation level and promotion of cell apoptosis caused by miR-1306-5p overexpression. Moreover, overexpression of HSD17B7 activated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) axis in HG-treated cells. In conclusion, quercetin inhibits ER stress and improves testosterone secretion disorder through the miR-1306-5p/HSD17B7 axis in diabetic rats.

中文翻译：

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槲皮素通过 miR-1306-5p/HSD17B7 轴抑制糖尿病大鼠的内质网应激，从而改善睾酮分泌障碍。

睾丸损伤和睾酮分泌障碍与糖尿病有关。槲皮素是一种常见的类黄酮，具有抗氧化、抗癌和降低血糖的作用。因此，本研究旨在在体内和体外研究槲皮素对糖尿病雄性大鼠生殖系统的影响，并阐明其作用机制。链脲佐菌素 (STZ) 诱导用于在 40 只雄性 Sprague Dawley (SD) 大鼠中建立糖尿病模型，随后给予 20 或 50 mg/kg 槲皮素。大鼠睾丸的睾丸间质细胞用高糖 (HG) 处理，然后用 5 或 10 μM 槲皮素处理。两剂槲皮素可增加大鼠体重和睾丸重量，降低血糖，抑制氧化应激。RT-qPCR 和蛋白质印迹显示槲皮素可减轻 STZ 诱导的睾丸损伤并促进睾酮合成。两种剂量的槲皮素都降低了 ROS 和 MDA 水平，并增加了 HG 处理的细胞中的 SOD 水平。体内和体外结果均证实，高剂量的槲皮素更有效。MiR-1306-5p 在糖尿病大鼠的睾丸组织和 HG 处理的细胞中上调。17β-羟基类固醇脱氢酶 (HSD17B7) 是 miR-1306-5p 的靶标，HSD17B7 在 STZ 诱导的大鼠组织和 HG 处理的细胞中下调。HSD17B7 过表达逆转了由 miR-1306-5p 过表达引起的 C/EBP 同源蛋白 (CHOP) 和葡萄糖调节蛋白 78 (Grp78) 蛋白水平以及 eIF2α 磷酸化水平和促进细胞凋亡的增加。而且，HSD17B7 的过表达激活了 HG 处理的细胞中的 Janus 激酶 2 (JAK2)/信号转导和转录激活因子 3 (STAT3) 轴。总之，槲皮素通过 miR-1306-5p/HSD17B7 轴在糖尿病大鼠中抑制 ER 应激并改善睾酮分泌障碍。