目的 通过建立小鼠治疗免疫检查点抑制剂相关结肠炎模型,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。
Abstract
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 To divide 36 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. Results The CMO group showed the epithelial cell necrosis and shedding, extensive edema, thinning of the intestinal wall, disordered glandular arrangement, severe ulcer symptoms, and extensive infiltration of inflammatory cells in the mucosal layer compared with the CON group. The colonic epithelial conditions and ulcer symptoms showed that the BBD group had reduced symptoms, moderate infiltration of inflammatory cells in the mucosal muscle layer, and no severe ulcer symptoms between the DSS and BBD group mice. Compared with the CON group,The weight, colon length, and colon coefficient of mice in other groups, decreased or became shorter. However. The weight, colon length, and colon coefficient of mice in the BBD group decreased or became shorter than in the MOD group and DSS group. The spleen coefficient of mice in the MOD group and DSS group decreased or became shorter compared in the CON group. The BBD group mice showed similar weight loss scores and stool shape score compared with the DSS group, while the fecal blood score and DAI score showed a decreasing trend. The mice of BBD group showed a decreasing trend in weight loss score, stool shape score, rectal bleeding score, and DAI score, as well as a decreasing trend in rectal bleeding score and DAI score compared with the MOD group. Conclusions This article constructs an immune checkpoint inhibitor associated colitis model by using immune checkpoint inhibitors, and feeding Baodan can significantly alleviate the symptoms of immune checkpoint inhibitor associated colitis in mice.
关键词
八宝丹 /
免疫检查点抑制剂 /
结肠炎 /
影响
Key words
Babao Dan /
Immune checkpoint inhibitors /
Colitis /
Influence
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