Department of Nephrology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital) and Nanchong Key Laboratory of Basic Science and Clinical Research on Chronic Kidney Disease, Nanchong, China.
Department of Gynaecology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital), Nanchong, China.
Acta Biochim Pol. 2023 Nov 29;70(4):891-897. doi: 10.18388/abp.2020_6778.
Diabetic nephropathy (DN), a microvascular complication of diabetes, increases the risk of all-cause diabetes and cardiovascular mortalities. Moreover, oxidative stress and pyroptosis play important roles in the pathogenesis of DN. Rhubarb is widely used in traditional medicine, and chrysophanol (Chr), a free anthraquinone compound abundant in rhubarb, exhibits potent antioxidant properties and ameliorates renal fibrosis. Therefore, this study aimed to investigate the effects of Chr on renal injury, oxidative stress, and pyroptosis in mice with DN. A DN model was established by feeding the mice a high-sugar and fat diet and injecting them with 50 mg/kg streptozotocin as a positive control. The DN mice had significantly impaired renal function, thickened glomerular thylakoids and basement membranes, increased fibrous tissue, and inflammatory cell infiltration. Superoxide dismutase (SOD) levels were reduced, malondialdehyde (MDA) levels were increased, interleukin (IL)-1β and IL-18 increased, and cleaved caspase-1, caspase-1, and gasdermin D (GSDMD) involved in the process of pyroptosis were upregulated in DN. Kelch-like ECH-associated protein 1 (Keap1) expression was upregulated, and nuclear factor erythroid 2-related factor 2 (Nrf2) expression was downregulated. Compared to those in the DN group, the Chr-treated mice with DN had improved renal dysfunction, weakened glomerular thylakoid and basement membrane thickening, and reduced fibrous tissue proliferation and inflammatory cell infiltration. Additionally, Chr increased SOD levels, decreased MDA, IL-1β, and IL-18, down-regulated caspase-1, cleaved caspase-1, GSDMD, and Keap1 expression, and upregulated Nrf2 expression, which reversed the DN. Therefore, Chr reduced oxidative stress and pyroptosis in DNmice by activating the Keap1/Nrf2 pathway.
糖尿病肾病（DN）是糖尿病的一种微血管并发症，增加了全因糖尿病和心血管死亡率的风险。此外，氧化应激和细胞焦亡在 DN 的发病机制中起重要作用。大黄在传统医学中被广泛应用，其中丰富的游离蒽醌化合物大黄素（Chr）具有强大的抗氧化特性，并能改善肾纤维化。因此，本研究旨在探讨 Chr 对糖尿病肾病小鼠肾脏损伤、氧化应激和细胞焦亡的影响。通过给小鼠喂食高糖高脂饮食和注射 50mg/kg 链脲佐菌素来建立 DN 模型，作为阳性对照。DN 小鼠的肾功能明显受损，肾小球足突和基底膜增厚，纤维组织增多，炎症细胞浸润。超氧化物歧化酶（SOD）水平降低，丙二醛（MDA）水平升高，白细胞介素（IL）-1β和 IL-18 增加，参与细胞焦亡过程的半胱氨酸天冬氨酸蛋白酶-1（caspase-1）、caspase-1 和 Gasdermin D（GSDMD）被上调。Kelch-like ECH-associated protein 1（Keap1）表达上调，核因子红细胞 2 相关因子 2（Nrf2）表达下调。与 DN 组相比，DN 合并 Chr 治疗的小鼠肾功能改善，肾小球足突和基底膜增厚减弱，纤维组织增生和炎症细胞浸润减少。此外，Chr 增加了 SOD 水平，降低了 MDA、IL-1β和 IL-18，下调了 caspase-1、cleaved caspase-1、GSDMD 和 Keap1 的表达，上调了 Nrf2 的表达，逆转了 DN。因此，Chr 通过激活 Keap1/Nrf2 通路减少了 DNMice 中的氧化应激和细胞焦亡。
