Department of Medical Laboratory Diagnosis Lecturer, Quanzhou Medical College, Quanzhou, Fujian Province, China.
The Second Attached Hospital of Fujian Medical University, Quanzhou, Fujian Province, China.
Tissue Cell. 2023 Dec;85:102229. doi: 10.1016/j.tice.2023.102229. Epub 2023 Sep 29.
Doxorubicin is an anthracycline antitumor agent commonly used in clinical practice, which has some nephrotoxicity and is often used to establish mouse models of kidney injury for basic medical research. This study will investigate the protective effect of quercetin on renal function in doxorubicin-induced nephropathy mice.
C57BL/6 mice were divided into control, model, and quercetin low-, and high-dose groups. Serum and urine were collected to analyze markers of kidney function. H&E staining was used to detect pathological changes in renal tissues. Transmission electron microscopy was performed to observe the ultrastructural changes in renal tissues. Immunohistochemistry was performed to detect the changes of Ang II. RT-qPCR was performed to detect the changes of cytokines. ELISA was used to detect changes in serum inflammatory factors. Molecular docking was performed to verify the targeting relationship between quercetin and AKT1. Western blot was performed to detect Bax, Bcl-2, Cyt-c, AKT1, Raf, MEK, and ERK proteins.
Quercetin could induce the recovery of kidney function in kidney-injured mice; H&E results showed that kidney tissue damage and tissue fibrosis were reduced in kidney-injured mice under quercetin. The mitochondrial swollen structure was destroyed by doxorubicin, while the mitochondrial structure was restored under quercetin. The levels of abnormal apoptotic proteins Bax and Bcl-2 were regulated to normal by quercetin. The high expression of Ang II caused by doxorubicin was down-regulated by quercetin. Abnormal inflammatory factors caused by doxorubicin were reversed by quercetin. Western blot experiments showed that quercetin regulated the protein levels of AKT1 and Raf/MEK/ERK and inhibited the detrimental effects of doxorubicin.
Quercetin may mitigate doxorubicin-induced kidney injury in mice by regulating renal cell inflammatory factors and Raf/MEK/ERK signaling pathway through AKT1 to promote recovery of renal function.
多柔比星是一种临床常用的蒽环类抗肿瘤药物，具有一定的肾毒性，常被用于建立基础医学研究的肾损伤小鼠模型。本研究将探讨槲皮素对多柔比星诱导的肾病小鼠肾功能的保护作用。
将 C57BL/6 小鼠分为对照组、模型组、槲皮素低剂量组和槲皮素高剂量组。收集血清和尿液，分析肾功能标志物。进行 H&E 染色，观察肾组织的病理变化。进行透射电镜观察，观察肾组织的超微结构变化。进行免疫组化，检测 Ang II 的变化。进行 RT-qPCR，检测细胞因子的变化。ELISA 用于检测血清中炎症因子的变化。分子对接验证槲皮素与 AKT1 的靶向关系。Western blot 检测 Bax、Bcl-2、Cyt-c、AKT1、Raf、MEK 和 ERK 蛋白。
槲皮素可诱导肾损伤小鼠肾功能恢复；H&E 结果显示，槲皮素可减少肾损伤小鼠肾组织损伤和组织纤维化。多柔比星导致线粒体肿胀结构破坏，而槲皮素可使线粒体结构恢复。槲皮素可调节 Bax 和 Bcl-2 等异常凋亡蛋白恢复正常。多柔比星引起的 Ang II 高表达被槲皮素下调。槲皮素可逆转多柔比星引起的异常炎症因子。Western blot 实验表明，槲皮素通过调节 AKT1 调节 Raf/MEK/ERK 信号通路，调节肾细胞炎症因子，抑制多柔比星的有害作用。
槲皮素可能通过调节 AKT1 调节 Raf/MEK/ERK 信号通路，抑制肾细胞炎症因子，促进肾功能恢复，减轻多柔比星诱导的小鼠肾损伤。
