机构地区:[1]福建中医药大学中西医结合研究院中西医结合学院,福建福州350122 [2]福建医科大学肿瘤临床医学院,福建省肿瘤医院,福建福州350014 [3]福建省中西医结合老年性疾病重点实验室,福建福州350122 [4]中西医结合基础福建省高校重点实验室,福建福州350122
出 处:《中国医药指南》2025年第12期1-5,共5页Guide of China Medicine
基 金:国家自然科学基金(82405100)。
摘 要:目的通过建立小鼠治疗免疫检查点抑制剂相关性结肠炎模型,探讨八宝丹(BBD)对小鼠免疫检查点抑制剂相关性结肠炎的影响。方法采用随机数字表法,将C57BL/6J小鼠分为4组,即空白组(CON组)、生理盐水组(DSS组)、生理盐水+抑制剂组(MOD组)、生理盐水+抑制剂+八宝丹组(BBD组),每组5只小鼠。造模干预期间每天称量小鼠体重,记录小鼠的饮水、摄食量。所有小鼠建模后,第10天采用代谢笼收集小鼠粪便,对小鼠进行腹泻评分、DAI评分,小鼠经1%戊巴比妥(70~80 mg/kg)腹腔注射处死后取血液和结肠组织,观察比较4组小鼠的结肠改变情况。结果MOD组与CON组小鼠上皮比较,上皮细胞坏死脱落、大面积水肿、肠壁变薄,腺体排列凌乱,溃疡症状严重,黏膜层大量炎细胞浸润;DSS与BBD组小鼠结肠上皮情况、溃疡症状比较,BBD组症状减轻,黏膜肌层中量炎细胞浸润,无严重溃疡症状。与CON组比较,MOD组、DSS组和BBD组小鼠的体重、结肠长度和结肠系数均下降或变短,但BBD组小鼠体重较MOD组、DSS组小鼠体重、结肠长度和结肠系数下降或变短的程度低,但与CON组比较,MOD组、DSS组和BBD组小鼠脾脏系数变大。BBD组小鼠与DSS组比较,体重下降分数、大便形状分数类似,便血分数、DAI评分均呈现降低趋势。BBD组小鼠与MOD组比较,体重下降分数、大便形状分数、便血分数、DAI评分均呈现下降趋势,便血分数、DAI评分均呈现降低趋势。结论本文通过采用免疫检查点抑制剂构建免疫检查点抑制剂相关性结肠炎模型,发现八宝丹干预可明显减轻小鼠免疫检查点抑制剂相关性结肠炎症状。Objective To establish a mouse model for treating immune checkpoint inhibitor associated colitis and explore the effect of Babao Dan on immune checkpoint inhibitor associated colitis in mice.Methods The C57BL/6J mice into four groups:blank group(CON group),saline group(DSS group),saline+inhibitor group(MOD group),and saline+inhibitor+Babao Dan group(BBD group),with 5 mice in each group by a random number table.During the modeling period,the mice were weighed daily,and their water and food intake were recorded.After modeling,the feces of all mice were collected on the 10th day in metabolic cages,and the mice were scored for diarrhea and DAI,and the mice were killed by 1%pentobarbital(70-80 mg/kg)intraperitoneally,and the blood and colon tissue were collected.Observe and compare the colonic changes in the 4 groups of mice.Results Comparing the epithelium of mice in the MOD group and the CON group,the epithelial cells were necrotic and detached,there was extensive edema,the intestinal wall was thinned,the arrangement of glands was disorganized,and there were serious symptoms of ulceration and a large number of inflammatory cells infiltrating the mucous layer;comparing the epithelium of the colons of mice in the DSS and the BBD groups and the symptoms of ulceration,the symptoms of the BBD group were alleviated,and the myometrial layer of the mucous membrane had a moderate amount of inflammatory cells infiltrating,and there were no serious symptoms of ulceration.Compared with the CON group,the body weight,colon length and colon coefficient of mice in the MOD,DSS and BBD groups decreased or became shorter,but the body weight of mice in the BBD group decreased or became shorter to a lesser extent than that of mice in the MOD,DSS groups,but the spleen coefficient of mice in the MOD,DSS and BBD groups became larger when compared with that of mice in the CON group.The body weight loss fraction,feces and fecal matter of mice in the BBD group were lower than that of mice in the DSS group,but the spleen coefficient of mice in
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