Chronic kidney disease (CKD) has a high incidence and poor prognosis; however, no effective treatment is currently available. Our previous study found that the improvement effect of the herb pair of Rhubarb-Astragalus on CKD is likely related to the inhibition of the TGF-β1/p38-MAPK pathway. In the present study, a p38-MAPK inhibitor was used to further investigate the inhibitory effect of Rhubarb-Astragalus on the TGF-β1/p38-MAPK pathway and its relationship with autophagy. A rat model of unilateral ureteral obstruction (UUO) was established, and a subgroup of rats was administered Rhubarb-Astragalus. Renal function and renal interstitial fibrosis (RIF) were assessed 21 d after UUO induction. , HK-2 cells were treated with TGF-β1 and a subset of cells were treated with Rhubarb-Astragalus or p38-MAPK inhibitor. Western blotting, immunohistochemistry, and qRT-PCR analyses were used to detect the relevant protein and mRNA levels. Transmission electron microscopy was used to observe autophagosomes. Rhubarb-Astragalus treatment markedly decreased the elevated levels of blood urea nitrogen, serum creatinine, and urinary N-acetyl-β-D-glucosaminidase; attenuated renal damage and RIF induced by UUO; and reduced the number of autophagosomes and lysosomes in UUO-induced renal tissues. Additionally, Rhubarb-Astragalus reduced the protein and mRNA levels of α-SMA, collagen I, LC3, Atg3, TGF-β1, p38-MAPK, smad2/3, and TAK1 in renal tissues of UUO rats. Rhubarb-Astragalus also reduced protein and mRNA levels of these indicators . Importantly, the effect of the p38-MAPK inhibitor was similar to that of Rhubarb-Astragalus. Rhubarb-Astragalus improves CKD possibly by downregulating autophagy via the p38-MAPK/TGF-β1 and p38-MAPK/smad2/3 pathways.

中文翻译：

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大黄黄芪对通过 p38-MAPK/TGF-β1 和 p38-MAPK/smad2/3 途径下调自噬来减轻肾间质纤维化

慢性肾脏病（CKD）发病率高，预后差；然而，目前尚无有效的治疗方法。我们前期研究发现大黄黄芪对CKD的改善作用可能与抑制TGF-β1/p38-MAPK通路有关。本研究采用p38-MAPK抑制剂进一步研究大黄黄芪对TGF-β1/p38-MAPK通路的抑制作用及其与自噬的关系。建立单侧输尿管梗阻（UUO）大鼠模型，并对一组大鼠给予大黄黄芪注射液。UUO 诱导后 21 天评估肾功能和肾间质纤维化 (RIF)。，HK-2 细胞用 TGF-β1 处理，部分细胞用大黄黄芪或 p38-MAPK 抑制剂处理。使用蛋白质印迹、免疫组织化学和qRT-PCR分析来检测相关蛋白和mRNA水平。使用透射电子显微镜观察自噬体。大黄黄芪治疗显着降低了升高的血尿素氮、血清肌酐和尿N-乙酰-β-D-氨基葡萄糖苷酶水平；减轻 UUO 引起的肾损伤和 RIF；并减少 UUO 诱导的肾组织中自噬体和溶酶体的数量。此外，大黄黄芪还能降低 UUO 大鼠肾组织中 α-SMA、胶原蛋白 I、LC3、Atg3、TGF-β1、p38-MAPK、smad2/3 和 TAK1 的蛋白质和 mRNA 水平。大黄黄芪还降低了这些指标的蛋白质和mRNA水平。重要的是，p38-MAPK 抑制剂的作用与大黄黄芪相似。大黄黄芪可能通过 p38-MAPK/TGF-β1 和 p38-MAPK/smad2/3 途径下调自噬来改善 CKD。