Li Yuan, Wu Tong, Li Hongye, Liu Mingming, Xu Haiyan
School of Basic Medicine, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.
Lianyungang Clinical School of Xuzhou Medical University, Lianyungang, 222006, People's Republic of China.
Diabetes Metab Syndr Obes. 2024 Jul 22;17:2709-2724. doi: 10.2147/DMSO.S464015. eCollection 2024.
Tanshinone IIA (Tan-IIA) is widely used in patients with diabetic nephropathy (DN), but its protective effect on podocytes in DN has not been well studied. In this study, the effects of Tan-IIA on autophagy and inflammation of glomerular podocytes in DN were observed in vivo and in vitro, and the underlying mechanisms were investigated. Irbesartan, an angiotensin II receptor blocker, is a representative medication for the clinical treatment of DN. So irbesartan was chosen as a positive control drug.
Eight-week-old male db/db mice were randomly divided into a DN group, an irbesartan group, and three groups receiving different doses of Tan-IIA. The control group consisted of the db/m littermate mice. Blood, urine, and kidney samples were taken from the mice after 12 weeks of continuous administration. Renal protection of Tan-IIA was evaluated using enzyme-linked immunosorbent assay kits, haematoxylin and eosin staining, transmission electron microscopy, Western blotting, and immunohistochemistry. In vitro, the protective effect of Tan-IIA on podocytes was explored using MPC5 cells cultured with high glucose.
Tan-IIA significantly improved renal pathological injury and relieved the renal dysfunction in DN. Compared with the DN group, Tan-IIA could up-regulate the expression of Synaptopodin, Podocin, LC3II/I and Beclin-1 ( < 0.05), and down-regulate the expression of p62, F4/80, NF-κB p65, IL-1β, TNF-α and IL-6 ( < 0.05) both in vivo and in vitro, suggesting that Tan-IIA treatment alleviated podocyte injury by promoting autophagy and inhibiting inflammation during DN. The levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in Tan-IIA group were lower than those in DN group ( < 0.05), indicating that Tan-IIA inhibited the PI3K/Akt/mTOR signalling pathway in podocytes, which was a key pathway in regulating both autophagy and inflammation.
Tan-IIA prevented podocyte injury in DN by fostering autophagy and inhibiting inflammation, at least in part via inhibition of the PI3K/Akt/mTOR signalling pathway.
丹参酮IIA（Tan-IIA）广泛应用于糖尿病肾病（DN）患者，但Tan-IIA对DN患者足细胞的保护作用尚未得到充分研究。本研究在体内和体外观察Tan-IIA对DN患者肾小球足细胞自噬和炎症的影响，并探讨其潜在机制。厄贝沙坦是一种血管紧张素II受体阻滞剂，是临床治疗DN的代表性药物。因此，选择厄贝沙坦作为阳性对照药物。
将8周龄雄性db/db小鼠随机分为DN组、厄贝沙坦组和接受不同剂量Tan-IIA的三组。对照组由db/m同窝小鼠组成。连续给药12周后从小鼠采集血液、尿液和肾脏样本。使用酶联免疫吸附测定试剂盒、苏木精和伊红染色、透射电子显微镜、蛋白质免疫印迹法和免疫组织化学法评估Tan-IIA的肾脏保护作用。在体外，使用高糖培养的MPC5细胞探索Tan-IIA对足细胞的保护作用。
Tan-IIA显著改善DN的肾脏病理损伤并缓解肾功能障碍。与DN组相比，Tan-IIA在体内和体外均可上调Synaptopodin、Podocin、LC3II/I和Beclin-1的表达（P<0.05），并下调p62、F4/80、NF-κB p65、IL-1β、TNF-α和IL-6的表达（P<0.05），表明Tan-IIA治疗通过促进自噬和抑制DN期间的炎症来减轻足细胞损伤。Tan-IIA组中p-PI3K/PI3K、p-Akt/Akt和p-mTOR/mTOR的水平低于DN组（P<0.05），表明Tan-IIA抑制足细胞中的PI3K/Akt/mTOR信号通路，这是调节自噬和炎症的关键通路。
Tan-IIA通过促进自噬和抑制炎症来预防DN中的足细胞损伤，至少部分是通过抑制PI3K/Akt/mTOR信号通路实现的。
