丹皮酚对5-FU诱导的小鼠肠道黏膜损伤的保护作用及对其抗肿瘤活性的影响

Protective effect of paeonol on intestinal mucosal injury induced by 5-fluorouracil in mice and its antitumor activity

目的研究丹皮酚对5-氟尿嘧啶(5-FU)诱导小鼠肠黏膜损伤中的保护作用。方法SD成年雄性C57BL/6J小鼠随机分为对照组(Con组,12只)、5-FU注射组(5-FU组,12只)、丹皮酚25 mg/kg组(5-FU+Pae 25 mg/kg组,13只)、丹皮酚100 mg/kg组(5-FU+Pae 100 mg/kg组,13只)。通过腹腔注射5-FU建立小鼠肠黏膜损伤模型,探讨丹皮酚对小鼠5-FU注射后体重的影响。HE染色观察丹皮酚对小鼠小肠绒毛损伤的形态学影响;免疫组化实验研究小鼠小肠腺细胞凋亡情况;成瘤实验观察丹皮酚对5-FU抗肿瘤活性的影响。结果注射5-FU 9天后,小鼠体重显著降低,而丹皮酚处理后可显著恢复小鼠体重。丹皮酚可明显降低小肠水肿程度或出血,并使小肠绒毛升高,增加小肠腺细胞数量。免疫组化结果显示,丹皮酚可显著降低小肠腺细胞凋亡程度。结论丹皮酚可通过抑制小肠腺细胞凋亡降低5-FU对小鼠黏膜损伤的影响,具有一定的抗肿瘤作用,并可增强其抗肿瘤活性。

Objective To study the protective effect of Paeonol on intestinal mucosal injury induced by 5-FU in mice.Methods Mice were randomly divided into control group(CON,12 mice),5-FU injection group(5-FU,12 mice),paeonol 25mg/kg group(5-FU+25mg/kg Pae,13 mice),paeonol 100mg/kg group(5-FU+100mg/kg Pae,13 mice).The mice intestinal mucosal injury model was established by intraperitoneal injection of 5-FU,and the effects of paeonol on the weight of mice after 5-FU injection were studied.The morphological effects of paeonol on the small intestinal villus injury were observed by H&E staining,and the apoptosis of small intestinal adenocytes was studied by immunohistochemical experiment.Finally,the effect of paeonol on 5-FU antitumor activity was observed by tumorigenicity assay.Results After 9 days of 5-FU injection,the weight of mice decreased significantly,while paeonol could significantly restore the weight of mice.Paeonol can significantly reduce the degree of small intestinal edema or bleeding,and increase the number of small intestinal glands.Immunohistochemical results showed that paeonol could significantly reduce the apoptosis of small intestinal gland cells.Finally,we found that paeonol had certain anti-tumor effects and might enhance the anti-tumor activity of 5-FU.Conclusion Paeonol can reduce the effect of 5-FU on mucosal injury and enhance the pit tumor activity of mice by inhibiting the apoptosis of small adenocarcinoma cells.