With the increasing incidence of chronic kidney disease (CKD), the development of safe and effective anti-renal fibrosis drugs is particularly urgent. Recently, Baicalin has been considered to have a renal protective effect, but its bioavailability is too low. Therefore, we synthesized baicalin-2-ethoxyethyl ester (BAE) by esterification of baicalin. We hope that this experiment will demonstrate the anti-renal fibrosis effect of BAE and explain its molecular mechanism. In this study, the chronic kidney injury model of SD rats was established by 5/6 nephrectomy, and BAE was given for 28 days. The results showed that after BAE treatment, the serum creatinine and urea nitrogen levels decreased significantly, and the pathological changes in kidneys were improved. In addition, RNA-seq analysis showed that the mechanism of BAE in relieving renal fibrosis was related to the ECM receptor, PI3K/AKT signaling pathway, and inflammatory reaction. The western blotting analysis confirmed that BAE could inhibit the expression of α-SMA, TGF-β1, p-PI3K, p-AKT, p-IκBα, and NF-κB p65. We found that BAE can inhibit the inflammatory reaction and promote the degradation of the extracellular matrix by inhibiting the activation of the PI3K/AKT/NF-κB pathway, thus alleviating the symptoms of renal fibrosis in 5/6Nx rats, which revealed BAE was a potential compound to relieve renal fibrosis effect.

随着慢性肾脏病（CKD）发病率的不断上升，开发安全有效的抗肾纤维化药物显得尤为迫切。近年来，黄芩苷被认为具有肾保护作用，但其生物利用度太低。因此，我们通过黄芩苷酯化合成了黄芩苷-2-乙氧基乙酯（BAE）。我们希望这个实验能够证明BAE的抗肾纤维化作用并解释其分子机制。本研究采用5/6肾切除术建立SD大鼠慢性肾损伤模型，并给予BAE治疗28 d。结果显示，BAE治疗后，血清肌酐和尿素氮水平显着下降，肾脏病理变化得到改善。此外，RNA-seq分析显示BAE缓解肾纤维化的机制与ECM受体、PI3K/AKT信号通路、炎症反应有关。Western blotting分析证实BAE可以抑制α-SMA、TGF-β1、p-PI3K、p-AKT、p-IκBα和NF-κB p65的表达。我们发现BAE可以通过抑制PI3K/AKT/NF-κB通路的激活来抑制炎症反应并促进细胞外基质的降解，从而减轻5/6Nx大鼠肾纤维化的症状，这表明BAE是一种具有缓解肾纤维化作用的潜在化合物。