首页|乌梅丸通过调控NLRP3炎症小体改善溃疡性结肠炎大鼠肠黏膜炎症反应及细胞焦亡

乌梅丸通过调控NLRP3炎症小体改善溃疡性结肠炎大鼠肠黏膜炎症反应及细胞焦亡

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目的:研究乌梅丸通过调控NOD 样受体热蛋白结构域3(NLRP3)炎症小体改善溃疡性结肠炎(UC)大鼠肠黏膜炎症反应及细胞焦亡的作用及机制.方法:选择雄性SD大鼠进行动物实验,采用2,4,6-三硝基苯磺酸灌肠的方式建立UC模型,造模后给予不同剂量乌梅丸灌胃,阴性对照(NC)-慢病毒(LV)或NLRP3-LV尾静脉注射.评价各组大鼠疾病活动指数(DAI),测量结肠长度,检测病理改变及组织病理评分、结肠组织IL-1β、IL-18含量及GSDMD-N、NLRP3、Cleaved caspase-1表达.结果:UC组大鼠结肠黏膜出现典型UC病理改变,DAI、组织病理评分、结肠组织IL-1β、IL-18含量及GSDMD-N、NLRP3、Cleaved caspase-1表达高于对照组,结肠长度短于对照组(P<0.05);不同浓度乌梅丸组大鼠结肠黏膜UC病理改变改善,DAI、组织病理评分、结肠组织IL-1β、IL-18含量及GSDMD-N、NLRP3、Cleaved caspase-1表达低于UC组,结肠长度长于UC组(P<0.05);高剂量乌梅丸灌胃同时注射LV,NLRP3-LV+UC+高剂量乌梅丸组大鼠结肠黏膜UC病理改变加重,DAI、组织病理评分、结肠组织IL-1β、IL-18含量及GSDMD-N、NLRP3、Cleaved caspase-1表达高于NC-LV+UC+高剂量乌梅丸组,结肠长度短于NC-LV+UC+高剂量乌梅丸组(P<0.05).结论:乌梅丸通过抑制NLRP3炎症小体改善UC大鼠肠黏膜炎症反应及细胞焦亡.
Wu-Mei-Wan improves colonic mucosal inflammation and pyroptosis in rats with ulcerative colitis via regulating NLRP3 inflammasome
Objective:To study effect and mechanism of Wu-Mei-Wan on improving colonic mucosal inflammatory response and pyroptosis in rats with ulcerative colitis(UC)via regulating NOD-like receptor family pyrin domain containing 3(NLRP3)inflam-masome.Methods:Male SD rats were selected for animal experiments.UC model was established by enema with 2,4,6-trinitroben-zene sulfonic acid.After model was established,different doses of Wu-Mei-Wan were given by gavage,negative control(NC)-lentivi-rus(LV)or NLRP3-LV were injected by tail vein.Disease activity index(DAI)of rats in each group was evaluated,length of colon was measured,pathological changes and histopathological scores,contents of IL-1β,IL-18,GSDMD-N,NLRP3 and Cleaved cas-pase-1 expressions in colon tissues were detected.Results:Typical UC pathological changes were found in colon mucosa of UC group,DAI,histopathological score,IL-1β,IL-18 contents,GSDMD-N,NLRP3 and Cleaved caspase-1 expressions in colon tissues of UC group were higher than control group,and colon length was shorter than control group(P<0.05).UC pathological changes of colon mucosa of rats in different concentrations of Wu-Mei-Wan groups were improved,DAI,histopathological score,IL-1β,IL-18 con-tents,GSDMD-N,NLRP3 and Cleaved caspase-1 expressions in colon tissues were lower than UC group,and colon length was longer than UC group(P<0.05).LV was injected simultaneously with intragastric administration of high-dose Wu-Mei-Wan,pathological changes of UC in colon mucosa of rats in NLRP3-LV+NC+high-dose Wu-Mei-Wan group was aggravated,DAI,histopathological score,IL-1β,IL-18 contents,GSDMD-N,NLRP3 and Cleaved caspase-1 expressions in colon tissues were higher than NC-LV+NC+ high-dose Wu-Mei-Wan group,and colon length was shorter than NC-LV+NC+high-dose Wu-Mei-Wan group(P<0.05).Conclusion:Wu-Mei-Wan improves colonic mucosal inflammation and pyroptosis in UC rats by inhibiting NLRP3 inflammasome.

Ulcerative colitisWu-Mei-WanNLRP3 inflammasomeInflammatory responsePyroptosis

李克亚、王真权、王军文

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湖南中医药大学第二附属医院肛肠科,长沙 410005

湖南中医药大学国际教育学院,长沙 410208

溃疡性结肠炎 乌梅丸 NLRP3炎症小体 炎症反应 细胞焦亡

湖南省中医药科研计划(2022)湖南省自然科学基金青年基金(2022)

D20220352022JJ40325

2024

中国免疫学杂志
中国免疫学会,吉林省医学期刊社

中国免疫学杂志

CSTPCD北大核心
影响因子:0.926
ISSN:1000-484X
年,卷(期):2024.40(1)
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