■丹参酮IIA(Tan-IIA)广泛用于糖尿病肾病(DN)患者,但其对DN足细胞的保护作用尚未得到很好的研究。在这项研究中,观察Tan-IIA对DN肾小球足细胞自噬和炎症的影响,并对其潜在机制进行了研究。厄贝沙坦,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,三组接受不同剂量的Tan-IIA。对照组由db/m同窝小鼠组成。血,尿液,在连续给药12周后从小鼠中采集肾脏样品。使用酶联免疫吸附测定试剂盒评估Tan-IIA的肾脏保护作用,苏木精和伊红染色,透射电子显微镜,西方印迹,和免疫组织化学。体外,使用高糖培养的MPC5细胞研究了Tan-IIA对足细胞的保护作用。
■Tan-IIA可明显改善DN的肾脏病理损伤,减轻肾功能损害。与DN组相比,Tan-IIA可以上调突触素的表达,Podocin,LC3II/I和Beclin-1(p<0.05),下调p62、F4/80、NF-κBp65、IL-1β的表达,TNF-α和IL-6(p<0.05)在体内和体外,提示Tan-IIA治疗可通过促进自噬和抑制炎症反应减轻足细胞损伤。p-PI3K/PI3K的水平,Tan-IIA组的p-Akt/Akt和p-mTOR/mTOR均低于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途径。
■Tan-IIA通过促进自噬和抑制炎症来预防DN足细胞损伤,至少部分通过抑制PI3K/Akt/mTOR信号通路。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 (p < 0.05), and down-regulate the expression of p62, F4/80, NF-κB p65, IL-1β, TNF-α and IL-6 (p < 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 (p < 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.
UNASSIGNED: 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.