Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing 100853, China.
School of Medicine, Nankai University, Tianjin 300071, China.
Biomed Pharmacother. 2023 Sep;165:115233. doi: 10.1016/j.biopha.2023.115233. Epub 2023 Aug 1.
Shenhua tablet (SH), a formulation of traditional Chinese medicine, exerts renoprotective effect on chronic kidney diseases, and it has been found to restrain inflammation, but the mechanism is still unclear. Here, we explored the potential renoprotection of SH in mesangial proliferative glomerulonephritis (MsPGN) rat model induced by anti-Thy1 antibody. Administration of SH reduced urinary albumin/creatinine ratio (UACR) and significantly attenuated mesangial cell proliferation and renal inflammation. Notably, SH protected rats against renal inflammation, which was associated with decreasing macrophage infiltration and promoting macrophage anti-inflammatory activity. Network analysis combined with arrays identified the Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling pathway as the main pathways of SH could target inflammation. Furthermore, it was confirmed that mesangial cell proliferation, which response to inflammation, were alleviated by ASS1 expression enhanced after SH administration both in vivo and in vitro. Collectively, SH has the beneficial on relieving the progression of MsPGN to alleviate inflammation and mesangial proliferation by inhibiting STAT3 phosphorylation and maintains the expression level of ASS1, might be an effective strategy for treating MsPGN.
肾华片(SH)是一种中药配方,对慢性肾脏病有肾保护作用,已被发现能抑制炎症,但机制尚不清楚。在这里,我们在抗 Thyl 抗体诱导的系膜增生性肾小球肾炎(MsPGN)大鼠模型中探索了 SH 的潜在肾保护作用。SH 的给药降低了尿白蛋白/肌酐比值(UACR),并显著减轻了系膜细胞增殖和肾脏炎症。值得注意的是,SH 保护大鼠免受肾脏炎症的影响,这与减少巨噬细胞浸润和促进巨噬细胞抗炎活性有关。网络分析结合阵列确定了 Janus 激酶信号转导和转录激活因子(JAK-STAT)信号通路是 SH 可以靶向炎症的主要途径。此外,还证实 SH 给药后,ASS1 表达增强,体内和体外炎症反应引起的系膜细胞增殖均得到缓解。综上所述,SH 通过抑制 STAT3 磷酸化和维持 ASS1 的表达水平,对缓解 MsPGN 的进展有有益作用,从而减轻炎症和系膜增殖,可能是治疗 MsPGN 的有效策略。