丹皮酚对5-氟尿嘧啶诱导的小鼠肠道黏膜炎的保护作用及其机制研究  

Protective effect of paeonol on 5-FU-induced intestinal mucositis in mice

作　　者：冯筱璐[1] 王娅宁[1] 白宝平[1] 岳鹏莹[1] 何敏[1] 胡建新 FENG Xiao-lu;WANG Ya-ning;BAI Bao-ping;YUE Peng-ying;HE Min;HU Jian-xin(Xi'an Innovation College,Yan'an University,Xi'an 710100,Shaanxi,China)

机构地区：[1]延安大学西安创新学院,陕西西安710100

出　　处：《毒理学杂志》2021年第4期316-321,共6页Journal of Toxicology

基　　金：2020年度陕西省教育厅专项科学研究计划(20JK1001)。

摘　　要：目的研究丹皮酚对5-氟尿嘧啶(5-FU)诱导的小肠道黏膜炎的保护作用及其机制。方法45只BALB/c小鼠随机分为5组:对照组、模型组、低剂量组、中剂量组和高剂量组。模型组低、中和高剂量组腹腔注射5-氟尿嘧啶50 mg/kg·bw,连续给药5 d;对照组给予注射相应体积磷酸盐缓冲液(PBS);低、中、高剂量组分别在腹腔注射5-FU前2 d开始经口灌胃丹皮酚12.5、25和50 mg/kg·bw,2次/d,连续7 d,对照组和模型组给予相应体积蒸馏水灌胃;记录小鼠体重和观测小鼠每日的大便情况;将小鼠处死后,取空肠进行切片、苏木素-伊红(HE)染色,并测量其绒毛高度和隐窝深度,计算绒毛高度/隐窝深度比值;采用气相色谱火焰离子化检测器(GC-FID)检测肠内容物中短链脂肪酸含量;采用ELISA法检测小肠组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)含量;Western blot实验检测小肠组织NF-κB通路相关蛋白TLR4、NF-κB p65和p-NF-κB p65的表达水平。结果相较模型组,3组给药组第4天体重下降程度出现明显抑制,差异有统计学意义(P<0.05或P<0.01),大便得分第3天开始出现明显升高(P<0.01);HE染色发现模型组小肠绒毛形态萎缩、淡染和损伤较为严重,3组给药组出现与模型组类似的现象,但随着剂量的增加,小肠绒毛状况逐渐好转;3组给药组的小鼠绒毛高度明显降低(P<0.01),隐窝深度明显增加(P<0.01),小鼠绒毛高度/隐窝深度比值明显升高(P<0.01);3组给药组小鼠盲肠内容物中4种短链脂肪酸含量明显升高(P<0.01);3组给药组小肠组织中NF-α、IL-1β和IL-6含量明显低于模型组(P<0.01);3组给药组NF-κB p65表达差异无统计学意义(P>0.05),TLR4和p-NF-κB p65表达均明显上调(P<0.01),且具一定剂量效应关系。结论丹皮酚通过激活TLR4/NF-κB通道,抑制炎症因子的释放,保护5-氟尿嘧啶诱导的小鼠肠道黏膜炎。Objective To study the protective effect of paeonol on 5-fluorouracil(5-FU)-induced small intestinal mucositis and its mechanism.Methods Forty-five BALB/c mice were randomly divided into five groups:control group,model group,low-dose group,middle-dose group and high-dose group;model group and low-dose,medium-dose and high-dose groups were intraperitoneally injected with 50 mg/kg·bw 5-FU for five days.The control group was injected with corresponding volume of PBS.The low-dose,medium-dose and high-dose groups were orally gavaged 12.5,25 and 50 mg/kg·bw paeonol twice a day for consecutive seven days,which was two days before the intraperitoneal injection of 5-FU.The control group and model group were given the corresponding volume of distilled water by gavage.The weights of the mouse were recorded and the daily stool of the mouse were observed.After the mouses were sacrificed,the jejunum was taken to perform sectioning,HE staining,and measure the villus height and crypt depth,calculate the ratio of villus height/crypt depth;gas chromatography flame ionization detector(GC-FID)was used to detect the content of short-chain fatty acids in the intestinal content;the contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were detected by ELISA in the small intestine tissue;Western blot was used to detect NF-κB pathway related proteins TLR4,NF-κB p65 and p-NF-κB p65 in small intestine tissue.Results Compared with the model group,the weight loss of the three groups was significantly inhibited on the 4 th day(P<0.05 or P<0.01),and the stool score began to increase significantly on the 3 rd day(P<0.01);the small intestinal villi of mice in model group were atrophied,lightly stained and damaged more severely,and the similar phenomena were doserved in three dose groups,but with the dose increase of paeonol,the condition of small intestinal villi gradually improved;the mice in the three dose groups had significant villi decrease(P<0.01),the crypt depth increased significantly(P<0.01),and

关 键 词：丹皮酚 5-氟尿嘧啶 肠道粘膜炎 NF-κB通道 

分 类 号：R574[医药卫生—消化系统] R99[医药卫生—内科学]