Ma Yingrui, Bai Bufan, Liu Deng, Shi Rong, Zhou Qianmei
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Department of Intensive Care Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Breast Cancer (Dove Med Press). 2024 Aug 16;16:451-469. doi: 10.2147/BCTT.S475860. eCollection 2024.
Shenqi Fuzheng Injection (SQFZ) is a traditional Chinese medicine injection consists of extracts of and . 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.
参芪扶正注射液（SQFZ）是一种由[具体成分1]和[具体成分2]提取物组成的中药注射液。将SQFZ与传统化疗相结合可能会提高治疗效果并减少化疗的副作用。然而，SQFZ减轻顺铂诱导的肾损伤的机制仍不清楚。
通过超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）技术鉴定SQFZ的主要化合物。使用多个数据库预测SQFZ的潜在靶点。通过将4T1细胞注射到小鼠体内建立乳腺癌模型。观察肿瘤生长和体重。测量血清血尿素氮（BUN）、肌酐（CRE）和谷胱甘肽（GSH）水平。通过苏木精-伊红染色（HE）测量其肾损伤程度。使用Hoechst33258染色、流式细胞术和TUNEL鉴定细胞凋亡。通过免疫组织化学（IHC）评估H2AX和干扰素基因刺激因子（STING）的表达，并通过蛋白质印迹分析评估凋亡相关蛋白。我们还评估了线粒体功能。使用酶联免疫吸附测定（ELISA）观察血清中炎性细胞因子的分泌。观察STING通路在单独暴露于顺铂或与SQFZ联合的HK-2肾小管上皮细胞中的作用。
SQFZ对肾损伤的潜在靶点主要与炎症反应、氧化与抗氧化、凋亡以及IFN信号通路有关。顺铂显著降低动物体重，而SQFZ与顺铂联合使用时体重无变化。SQFZ抵消了顺铂诱导的BUN和CRE升高。SQFZ改善了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磷酸鸟苷-磷酸腺苷合酶（cGAS）/STING信号通路激活。它还改善了顺铂诱导的线粒体功能障碍。
本研究结果表明，SQFZ通过抑制cGAS/STING信号通路有效减轻顺铂诱导的肾损伤。
