参芪扶正注射液通过 cGAS/STING 信号通路减轻乳腺癌小鼠模型中顺铂引起的肾损伤。
Shenqi Fuzheng Injection Reduces Cisplatin-Induced Kidney Injury via cGAS/STING Signaling Pathway in Breast Cancer Mice Model.
发表日期:2024
作者:
Yingrui Ma, Bufan Bai, Deng Liu, Rong Shi, Qianmei Zhou
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
参芪扶正注射液(SQFZ)是由党参和黄芪提取物组成的中药注射剂。 SQFZ与常规化疗相结合可以提高治疗效果并减少化疗的副作用。然而,SQFZ减轻顺铂肾损伤的机制仍不清楚。通过UPLC-Q-TOF-MS技术鉴定了SQFZ的主要化合物。使用多个数据库来预测 SQFZ 的潜在目标。我们通过将4T1细胞注射到小鼠体内建立了乳腺癌模型。观察肿瘤生长和体重。测量血清尿素氮(BUN)、肌酐(CRE)和谷胱甘肽(GSH)水平。通过苏木精-伊红染色(HE)测量肾损伤的程度。使用 Hoechst33258 染色、流式细胞术和 TUNEL 鉴定细胞凋亡。我们通过免疫组织化学 (IHC) 评估了 H2AX 和干扰素基因刺激物 (STING) 的表达,并通过蛋白质印迹分析评估了凋亡相关蛋白。我们还评估了线粒体功能。采用ELISA法观察血清中炎性细胞因子的分泌情况。顺铂单独或联合SQFZ对HK-2肾小管上皮细胞STING通路的影响。SQFZ对肾损伤的潜在靶点主要与炎症反应、氧化与抗氧化、细胞凋亡以及IFN信号通路有关。顺铂显着降低了动物体重,而 SQFZ 和顺铂的组合没有变化。 SQFZ 可以抵消顺铂引起的 BUN 和 CRE 升高。 SQFZ 改善顺铂诱导的氧化应激。它减少了顺铂诱导的细胞凋亡和线粒体 DNA 损伤,并逆转了顺铂诱导的环单磷酸鸟苷-单磷酸腺苷合酶 (cGAS)/STING 信号通路激活。它还可以改善顺铂引起的线粒体功能障碍。本研究结果表明,SQFZ 通过抑制 cGAS/STING 信号通路,有效减轻顺铂引起的肾损伤。© 2024 Ma et al.
Shenqi Fuzheng Injection (SQFZ) is a traditional Chinese medicine injection consists of extracts of Codonopsis pilosula and Astragalus mongholicus. Combining SQFZ with conventional chemotherapy may improve the therapeutic efficacy and reduce side-effects of chemotherapy. However, the mechanisms of SQFZ reducing cisplatin-induced kidney injury are still unclear.The main compounds of SQFZ were identified via UPLC-Q-TOF-MS technique. Using multiple databases to predict potential targets for SQFZ. We established a breast cancer model by injecting 4T1 cells into mice. Tumor growth and body weight were observed. Serum blood urea nitrogen (BUN), creatinine (CRE), and glutathione (GSH) levels were measured. The extent of their kidney injury was measured by hematoxylin-eosin staining (HE). Cell apoptosis was identified using Hoechst33258 staining, flow cytometry and TUNEL. We evaluated H2AX and stimulator of interferon genes (STING) expression by immunohistochemistry (IHC), and assessed apoptosis-associated proteins by Western blotting analysis. We also evaluated mitochondrial function. The secretion of the inflammatory cytokines in serum was observed using ELISA assay. The effect of the STING pathway in HK-2 renal tubular epithelial cells exposed to cisplatin alone or combined with SQFZ.The potential targets of SQFZ on kidney injury mainly related to inflammatory responses, oxidation and antioxidant, apoptosis as well as IFN signaling pathway. Cisplatin significantly reduced animal weight, while there were no changes in the combination SQFZ and cisplatin. SQFZ counteracted cisplatin-induced BUN and CRE elevation. SQFZ ameliorated the oxidative stress induced by cisplatin. It diminished cisplatin-induced apoptosis and mitochondrial DNA damage and reversed cisplatin-induced cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/STING signaling pathway activation. It also improved the mitochondrial dysfunction induced by cisplatin.The results of the present study suggested that SQFZ effectively reduced cisplatin-induced kidney injury by inhibiting cGAS/STING signaling pathway.© 2024 Ma et al.