Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.
Biomed Pharmacother. 2019 Oct;118:109223. doi: 10.1016/j.biopha.2019.109223. Epub 2019 Jul 17.
5-Fluorouracil (5-FU)-based chemotherapy often causes several drawbacks including weight loss, diarrhea, myelosuppression, and the intestinal mucositis. This study aimed to evaluate the protective effect of Qingjie Fuzheng Granule (QFG) on 5-FU-induced intestinal mucositis in CT-26 tumor-bearing xenograft mice and investigated the possible molecular mechanism.
Tumor xenograft models of CT-26 cells were generated in BALB/c nude mice, the mice were randomly divided into 4 groups including control, QFG, 5-FU and 5-FU combined QFG groups. The body weight, volume of tumor and diarrhea score of each group were recorded daily. On the fifth day, the blood of mice was collected, the mice were subsequently euthanized and their thymus, spleen, intestine and tumor were removed for the following analysis.
QFG alleviated severe diarrhea and reversed the decrease in the number of white blood cell including granulocyte and lymphocyte induced by 5-FU. QFG could also significantly improve 5-FU-induced several intestinal mucosal damages, and characterized by integrity villus and crypts, the reduction of necrotic cells. QFG decreased the serum levels of TNF-α, IL-1β, and IL-6 and increased the levels of IL-10. Furthermore, QFG inhibited the cellular apoptosis in the jejunum tissue caused by 5-FU via the increasing Bcl-2 expression and decreasing Bax expression. In addition, QFG promoted the cell proliferation via elevating the expression of Cyclin D1 and CDK4 and reducing p21 expression. Meanwhile, QFG could not further impact on the cell apoptosis and proliferation of tumors caused by 5-FU.
QFG attenuated the intestinal mucositis and diarrhea induced by 5-FU via preventive effect on inflammation and its improvement of the intestinal barrier function, inhibiting cell apoptosis and promoting cell proliferation, and without affecting the 5-FU treatment efficiency. The results suggest that QFG may act as a potential agent against chemotherapy-induced intestinal mucositis.
5-氟尿嘧啶（5-FU）为基础的化疗常引起多种不良反应，包括体重减轻、腹泻、骨髓抑制和肠道黏膜炎。本研究旨在评估清解扶正颗粒（QFG）对 CT-26 荷瘤异种移植小鼠 5-FU 诱导的肠道黏膜炎的保护作用，并探讨其可能的分子机制。
在 BALB/c 裸鼠中生成 CT-26 细胞的肿瘤异种移植模型，将小鼠随机分为 4 组，包括对照组、QFG 组、5-FU 组和 5-FU 联合 QFG 组。每天记录各组小鼠的体重、肿瘤体积和腹泻评分。第 5 天，采集小鼠血液，处死小鼠，取出其胸腺、脾、肠和肿瘤进行后续分析。
QFG 缓解了严重的腹泻，并逆转了 5-FU 引起的白细胞（包括粒细胞和淋巴细胞）数量减少。QFG 还可以显著改善 5-FU 引起的几种肠道黏膜损伤，表现为绒毛和隐窝完整，坏死细胞减少。QFG 降低了血清中 TNF-α、IL-1β 和 IL-6 的水平，增加了 IL-10 的水平。此外，QFG 通过增加 Bcl-2 的表达和降低 Bax 的表达，抑制了 5-FU 引起的空肠组织细胞凋亡。此外，QFG 通过提高 Cyclin D1 和 CDK4 的表达和降低 p21 的表达，促进了细胞增殖。同时，QFG 对 5-FU 引起的肿瘤细胞凋亡和增殖没有进一步影响。
QFG 通过预防炎症和改善肠道屏障功能、抑制细胞凋亡和促进细胞增殖来减轻 5-FU 引起的肠道黏膜炎和腹泻，而不影响 5-FU 的治疗效果。结果表明，QFG 可能是一种治疗化疗引起的肠道黏膜炎的潜在药物。
