School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, China.
The First Affiliated Hospital (School of Clinical Medicine), Guangdong Pharmaceutical University, Guangzhou, China.
Biomed Pharmacother. 2020 Nov;131:110699. doi: 10.1016/j.biopha.2020.110699. Epub 2020 Sep 2.
Xiao-Ban-Xia-Tang decoction (XBXT), an antiemetic formula in traditional Chinese medicine, has been proved to be a potential treatment for chemotherapy-induced nausea and vomiting (CINV), but the underlying mechanisms are not adequately understood. This study aimed to investigate changes in the ileum transcriptome after cisplatin and XBXT treatment and to reveal whether the antiemetic mechanisms of XBXT are related to its anti-inflammatory effect.
The pica model was established by a single intraperitoneal injection of 6 mg/kg cisplatin in Wistar rats. Tissues from the gastric antrum and ileum were stained with hematoxylin-eosin to observe gastrointestinal tract pathological changes. Based on the differentially expressed genes (DEGs) which were altered by cisplatin and reversed by XBXT, the transcriptome data of rat ileum were analyzed by GO, KEGG, and PPI analyses. Several inflammatory DEGs were validated by RT-PCR.
XBXT could reduce kaolin intake up to 72 h after modeling and alleviate the inflammatory damage of gastric antrum and ileum induced by cisplatin. According to the transcriptome profile, there were 75 DEGs down-regulated by cisplatin and up-regulated by XBXT and 343 DEGs up-regulated by cisplatin and down-regulated by XBXT. XBXT could blunt the overexpression of tryptophan hydroxylase 1 (the rate-limiting enzyme of serotonin synthesis) in ileum. Enrichment analysis showed that inhibiting overexpression of several conventional inflammation pathways and pro-inflammation cytokines were related to the antiemetic effectiveness of XBXT.
This study implies that inhibiting inflammatory signaling pathways and synthesis of serotonin might be potential mechanisms of XBXT's antiemetic effect against CINV.
消痞和胃汤（XBXT）是一种中药止吐方，已被证明是治疗化疗引起的恶心和呕吐（CINV）的潜在疗法，但作用机制尚不清楚。本研究旨在探讨顺铂和 XBXT 治疗后回肠转录组的变化，并揭示 XBXT 的止吐机制是否与其抗炎作用有关。
通过单次腹腔注射 6mg/kg 顺铂在 Wistar 大鼠中建立异食癖模型。用苏木精-伊红染色观察胃窦和回肠组织的胃肠道病理变化。基于顺铂改变且被 XBXT 逆转的差异表达基因（DEGs），通过 GO、KEGG 和 PPI 分析对大鼠回肠的转录组数据进行分析。通过 RT-PCR 验证了几个炎症 DEGs。
XBXT 可减少建模后 72 小时内的高岭土摄入量，并减轻顺铂引起的胃窦和回肠的炎症损伤。根据转录组谱，有 75 个 DEGs 被顺铂下调且被 XBXT 上调，343 个 DEGs 被顺铂上调且被 XBXT 下调。XBXT 可使回肠中色氨酸羟化酶 1（5-羟色胺合成的限速酶）的过表达减弱。富集分析表明，抑制几个常规炎症途径和促炎细胞因子的过表达与 XBXT 止吐作用的有效性相关。
本研究表明，抑制炎症信号通路和 5-羟色胺的合成可能是 XBXT 抗 CINV 止吐作用的潜在机制。
