Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China.
Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Front Cell Infect Microbiol. 2022 Aug 19;12:876781. doi: 10.3389/fcimb.2022.876781. eCollection 2022.
Studies show that traditional Chinese medicine (TCM), such as Liujunanwei (LJAW) decoction, can play important roles in alleviating side effects of chemotherapy. The purpose of this study was to understand how LJAW can counter chemotherapy-induced emesis alteration of gut microbiota. We evaluated the effect of LJAW on cisplatin (DDP)-induced nausea and vomiting using a rat-pica model. Rats react to emetic-producing stimuli with increased kaolin consumption, a phenomenon called pica. The rats were injected with cisplatin and then randomly assigned to the control (DDP), Ondansetron or LJAW. The intake of kaolin and chow diet as well as body weights were recorded every 24 hours. Fecal samples were collected prior to, after three and seven days of treatment. The expression of proteins was measured by western blot. The concentration of cytokines and serotonin was evaluated using ELISA assay kits. Kaolin consumption in rats induced by cisplatin was reduced by 16.5%, 22.5%, and 30.1% in the LJAW group compared to the DDP group at 24 hours, 48 hours and 72 hours, respectively (>0.05). LJAW significantly increased the food intake of the rats (13.94 ± 4.73 g) during the first 24 hours as opposed to the DDP (9.23 ± 3.77 g) (<0.05). 16S rRNA gene sequencing showed the abundance of increased in cisplatin treated rats. In addition, cisplatin injection caused an enrichment of s at the genus level. While, enrichment of and was presented in LJAW treated rats. Serotonin decreased in LJAW treated intestine and medulla oblongata tissues. Further, the protein expression of tryptophan hydroxylase 1 (TPH1) a rate limiting enzyme of serotonin was inhibited in LJAW treated rat's jejunum compared with cisplatin only treated rats. In addition, LJAW downregulated chemotherapy induced elevated inflammation. The results of this study indicated that LJAW is capable of decreasing cisplatin-induced kaolin intake in rat-nausea model (pica), which might be mediated through gut microbiome-induced anti-inflammation and anti-serotonin synthesis functions.
研究表明，中药（TCM），如六君子汤（LJAW），可以在缓解化疗副作用方面发挥重要作用。本研究旨在探讨 LJAW 如何对抗化疗引起的呕吐——肠道微生物群的改变。我们使用顺铂（DDP）诱导的大鼠嗜食模型评估了 LJAW 对顺铂诱导的恶心和呕吐的影响。当大鼠受到致吐刺激时，会增加高岭土的摄入，这一现象称为嗜食。大鼠注射顺铂后，随机分为对照组（DDP）、昂丹司琼或 LJAW 组。每 24 小时记录高岭土和饲料的摄入量以及体重。在治疗前、治疗后第 3 天和第 7 天收集粪便样本。通过 Western blot 测量蛋白质的表达。使用 ELISA 试剂盒评估细胞因子和 5-羟色胺的浓度。与 DDP 组相比，LJAW 组在 24 小时、48 小时和 72 小时时，顺铂诱导的大鼠高岭土消耗分别减少了 16.5%、22.5%和 30.1%（>0.05）。LJAW 组在第 1 天（13.94 ± 4.73 g）的食物摄入量明显高于 DDP 组（9.23 ± 3.77 g）（<0.05）。16S rRNA 基因测序显示，顺铂处理的大鼠中 丰度增加。此外，顺铂注射导致 s 在属水平上的富集。而 LJAW 处理的大鼠则表现出 和 的富集。LJAW 处理的肠道和延髓组织中 5-羟色胺减少。此外，LJAW 处理大鼠空肠组织中色氨酸羟化酶 1（TPH1）（5-羟色胺限速酶）的蛋白表达受到抑制，而 DDP 仅处理大鼠的蛋白表达未受抑制。此外，LJAW 下调了化疗引起的炎症反应。本研究结果表明，LJAW 能够降低顺铂诱导的大鼠厌食模型（嗜食）中高岭土的摄入，这可能是通过肠道微生物群诱导的抗炎和抗 5-羟色胺合成功能介导的。
