小檗胺通过抑制JAK2/STAT3信号通路改善小鼠溃疡性结肠炎
Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway
- 上海中医药大学学报 2023年37卷第2期 页码：14-21
- 作者机构：
1.上海中医药大学中药学院（上海 201203）
- 作者简介：
王鸿卿，男，硕士，实习研究员，主要从事中药药理学基础研究
范圣洁，副研究员，硕士生导师；E-mail：shengjiefan@shutcm.edu.cn
安叡，教授，硕士生导师；E-mail：anruimw@126. com
- 基金信息：上海市“科技创新行动计划”自然科学基金资助项目(19ZR1451900)
DOI：10.16306/j.1008-861x.2023.02.003
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王鸿卿,张丽君,林川等.小檗胺通过抑制JAK2/STAT3信号通路改善小鼠溃疡性结肠炎[J].上海中医药大学学报,2023,37(02):14-21.
WANG Hongqing,ZHANG Lijun,LIN Chuan,et al.Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(02):14-21.
王鸿卿,张丽君,林川等.小檗胺通过抑制JAK2/STAT3信号通路改善小鼠溃疡性结肠炎[J].上海中医药大学学报,2023,37(02):14-21. DOI： 10.16306/j.1008-861x.2023.02.003.
WANG Hongqing,ZHANG Lijun,LIN Chuan,et al.Berberine improves ulcerative colitis in mice by inhibiting JAK2/STAT3 signal pathway[J].Academic Journal of Shanghai University of Traditional Chinese Medicine,2023,37(02):14-21. DOI： 10.16306/j.1008-861x.2023.02.003.
摘要
目的,2,观察小檗胺（BBM）对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠的干预作用及其可能机制。,方法,2,①采用RAW264.7巨噬细胞炎症模型，考察BBM对其细胞活力、一氧化氮（NO）释放、肿瘤坏死因子-α（,TNF,⁃,α,）、白介素-1β（,IL,⁃,1β,）、,IL,⁃,6,和诱导型NO合酶（,iNOS,）炎症基因表达的影响。②雄性C57BL/6小鼠随机分为正常组、模型组、BBM组（50 mg/kg）和柳氮磺胺吡啶（SASP）阳性药组（250 mg/kg），每组8只。建立DSS诱导的UC小鼠模型，连续9 d灌胃给予相应药物。记录小鼠的体质量、脾脏系数、结肠长度及表观，评估疾病活动指数，HE染色观察结肠病理损伤；RT-qPCR检测小鼠结肠中炎症基因,TNF,⁃,α、IL,⁃,1β、IL,⁃,6、iNOS,的表达；Western blot检测小鼠结肠中紧密连接蛋白Claudin-4、Occludin及JAK2/STAT3通路蛋白的表达。,结果,2,①BBM对RAW264.7细胞活力没有明显影响（,P,>,0.05），但能呈剂量依赖性地减少细胞中NO的释放量（,P,<,0.05，,P,<,0.01）及炎症基因,TNF,⁃,α、IL,⁃,1β、IL,⁃,6、iNOS,的表达（,P,<,0.05，,P,<,0.01）；②BBM能改善UC小鼠的体质量下降和脾脏系数升高（,P,<,0.05）、抑制结肠的缩短（,P,<,0.05）、降低疾病活动指数评分和改善结肠病理损伤（,P,<,0.05）；③BBM能减少小鼠结肠中炎症基因,TNF,⁃,α、IL,⁃,1β、IL,⁃,6、iNOS,的表达（,P,<,0.05，,P,<,0.01）；④BBM能增加小鼠结肠中Claudin-4、Occludin的表达以及抑制JAK2和STAT3的磷酸化（,P,<,0.05，,P,<,0.01）。,结论,2,BBM能改善DSS诱导小鼠的UC，其作用机制可能为通过抑制JAK2/STAT3信号通路、减少炎症基因的表达，从而增强肠黏膜屏障功能。
Abstract
Objective： To observe the intervention effect and possible mechanism of berbamine （BBM） on ulcerative colitis （UC） mice induced by dextran sulfate sodium （DSS）.,Methods,2,①RAW264.7 macrophage inflammation model was used to investigate the effect of BBM on its cell viability， nitric oxide （NO） release， and the expression of tumor necrosis factor-α （,TNF,-,α,）， interleukin-1β （,IL,-,1β,）， ,IL,-,6, and inducible NO synthase （,iNOS,） inflammatory genes. ②Male C57BL/6 mice were randomly divided into normal group， model group， BBM group （50 mg/kg） and sulfasalazine （SASP） positive group （250 mg/kg）， with 8 mice in each group. DSS induced UC mouse model was established， and corresponding drugs were given by gavage for 9 d consecutively. The body mass， spleen coefficient， colon length and appearance of the mice were recorded， disease activity index was evaluated， and pathological injury of colon was observed by HE staining. The expression of inflammatory genes ,TNF,-,α， IL,-,1 β， IL,-,6 ,and ,iNOS, in the colon of mice were detected by RT-qPCR and the expression of tight junction proteins Claudin-4 and Occludin as well as JAK2/STAT3 pathway proteins were detected by Western blot.,Results,2,①BBM had no effect on RAW264.7 cells viability， but could reduce the NO release （,P,<,0.05，,P,<,0.01） and the expression of inflammatory genes, TNF,-,α,， ,IL,-,1β,，, IL,-,6 ,and, iNOS, in a dose-dependent manner （,P,<,0.05，,P,<,0.01）. ②BBM could improve the body mass loss and spleen coefficient increase of UC mice （,P,<,0.05）， inhibit the shortening of the colon （,P,<,0.05）， decrease the score of disease activity index and improve the pathological injury of colon in mice （,P,<,0.05）. ③BBM could reduce the expression of inflammatory genes ,TNF,-,α,， ,IL,-,1 β， IL,-,6, and, iNOS, in the colon of mice （,P,<,0.05，,P,<,0.01）. ④BBM could increase the expression of Claudin-4 and Occludin， and reduce the phosphorylation of JAK2 and STAT3 in the colon of mice （,P,<,0.05，,P,<,0.01）.,Conclusion,2,BBM can improve UC in mice induced by DSS， its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway and the reduction of inflammatory genes expression， thus enhancing the intestinal mucosal barrier function.
关键词
小檗胺溃疡性结肠炎JAK2/STAT3信号通路
Keywords
berbamineulcerative colitisJAK2/STAT3 signal pathway
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