Lu Jinhua, Lin Zechen, Huang Siyu, Shen Yiwei, Jiang Jing, Lin Shengyou
Department of Traditional Chinese Comprehensive Medical Oncology, Hangzhou Cancer Hospital, Hangzhou, China.
Oncology Department, Dingqiao Branch of GuangXing Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Evid Based Complement Alternat Med. 2020 Mar 12;2020:7901231. doi: 10.1155/2020/7901231. eCollection 2020.
Irinotecan (CPT-11) is used for therapy of various cancers. However, it has several serious adverse reactions such as diarrhea which is caused by SN-38, the active form of CPT-11. This study aimed to evaluate the effectiveness of Jiawei xianglian decoction (JWXLD), which has been widely used for the treatment of diarrhea in China. In this study, a mouse model with delayed diarrhea was generated by CPT-11. Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were performed to explore intestinal microflora and inflammatory cytokine. Hematoxylin and eosin (H&E) staining was used to analyze tissue morphology. We found that 0.12, 0.23, and 0.46 g JWXLD significantly reduced the severity of CPT-11-induced diarrhea. The levels of () and () were significantly downregulated by CPT-11, and these effects can be reversed by JWXLD treatment. Furthermore, JWXLD was observed to decrease the activity of -glucuronidase (-GD). Histopathological data showed that CPT-11 induced severe intestinal mucosal injury, which was characterized as grade 6, and JWXLD significantly alleviated the injury. In addition, CPT-11 increased the productions of tumor necrosis factor-alpha (TNF-), tumor necrosis factor-beta (TNF-), interleukin-6 (IL-6), and interleukin-1 (IL-1), but decreased interleukin-15 (IL-15), interleukin-7 (IL-7), and uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1). In conclusion, JWXLD can counteract these effects caused by CPT-11 treatment. JWXLD could alleviate CPT-11-induced diarrhea.
伊立替康(CPT-11)用于多种癌症的治疗。然而,它有一些严重的不良反应,如由CPT-11的活性形式SN-38引起的腹泻。本研究旨在评估在中国已广泛用于治疗腹泻的加味香连汤(JWXLD)的疗效。在本研究中,用CPT-11建立了迟发性腹泻小鼠模型。采用实时荧光定量聚合酶链反应(PCR)和酶联免疫吸附测定(ELISA)来探究肠道微生物群和炎性细胞因子。用苏木精-伊红(H&E)染色分析组织形态。我们发现0.12、0.23和0.46 g的JWXLD显著降低了CPT-11诱导的腹泻严重程度。CPT-11显著下调了()和()的水平,而JWXLD治疗可逆转这些作用。此外,观察到JWXLD降低了β-葡萄糖醛酸酶(β-GD)的活性。组织病理学数据显示,CPT-11诱导了严重的肠黏膜损伤,损伤程度为6级,而JWXLD显著减轻了该损伤。此外,CPT-11增加了肿瘤坏死因子-α(TNF-α)、肿瘤坏死因子-β(TNF-β)、白细胞介素-6(IL-6)和白细胞介素-1(IL-1)的产生,但降低了白细胞介素-15(IL-15)、白细胞介素-7(IL-7)和尿苷二磷酸葡萄糖醛酸基转移酶1A1(UGT1A1)。总之,JWXLD可以抵消CPT-11治疗引起的这些影响。JWXLD可以减轻CPT-11诱导的腹泻。