College of Biology Pharmacy and Food Engineering, Shangluo University, Beixin Street 10, Shangluo, China; Shaanxi Qinling Industrial Technology Research Institute of Special Biological Resources Co. Ltd, Beixin Street 10, Shangluo, China.
College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street 2888, Changchun, China.
Int Immunopharmacol. 2022 Feb;103:108466. doi: 10.1016/j.intimp.2021.108466. Epub 2021 Dec 18.
Most chemotherapeutic drugs can kill the tumor cells, but also cause a vast damage to body, such as intestinal mucositis (IM). The present study was design to find out the effect of Forsythiaside A (FTA) on chemotherapeutic-induced IM in rats. Briefly, for 3 consecutive days, male Sprague-Dawley rats were treated with 7 mg / kg methotrexate (MTX) to establish IM and simultaneously administered with 40 or 80 mg / kg FTA for 7 days. Our results showed that the final body weight and daily food intake were increased, and the disease activity index was reduced in the MTX group after FTA treatment. The MTX group showed the pathological alterations like the inflammatory cells infiltration, the mucosal layer destruction, glands expansion, intestinal villi structure disorder and goblet cells reduction, while we found that 80 mg / kg FTA treatment displayed evident reversal effects. ELISA further suggested that TNF-α, IL-1β and IL-18 levels in serum in MTX-induced rats were reduced after 80 mg / kg FTA treatment. Moreover, FTA decreased the number of leukocytes, neutrophils and lymphocytes in peripheral blood. Western blot and immunofluorescence results indicated that the expression levels of NLRP3, cleaved caspase 1, cleaved IL-1β and CD68 positive rate were down-regulated in MTX-induced rats after 80 mg / kg FTA intervention. The findings of the current study suggested that FTA effectively inhibited MTX-induced IM in rats by attenuating the activation of the NLRP3 signaling pathways.
大多数化疗药物可以杀死肿瘤细胞，但也会对身体造成广泛的损害，如肠黏膜炎（IM）。本研究旨在探讨连翘酯苷 A（FTA）对大鼠化疗诱导的 IM 的影响。简要地说，雄性 Sprague-Dawley 大鼠连续 3 天接受 7mg/kg 甲氨蝶呤（MTX）治疗以建立 IM，并同时给予 40 或 80mg/kg FTA 治疗 7 天。我们的结果表明，FTA 处理后 MTX 组的最终体重和每日食物摄入量增加，疾病活动指数降低。MTX 组表现出炎症细胞浸润、黏膜层破坏、腺体扩张、肠绒毛结构紊乱和杯状细胞减少等病理改变，而我们发现 80mg/kg FTA 治疗显示出明显的逆转作用。ELISA 进一步表明，80mg/kg FTA 处理后 MTX 诱导的大鼠血清中 TNF-α、IL-1β 和 IL-18 水平降低。此外，FTA 减少了外周血白细胞、中性粒细胞和淋巴细胞的数量。Western blot 和免疫荧光结果表明，80mg/kg FTA 干预后 MTX 诱导的大鼠 NLRP3、裂解的 caspase 1、裂解的 IL-1β 和 CD68 阳性率的表达水平下调。本研究的结果表明，FTA 通过抑制 NLRP3 信号通路的激活，有效抑制了 MTX 诱导的大鼠 IM。
