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黄芩汤通过调控内质网应激减轻小鼠溃疡性结肠炎

Huangqin Decoction alleviates ulcerative colitis in mice by reducing endoplasmic reticulum stress
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摘要 目的观察黄芩汤对小鼠溃疡性结肠炎(UC)细胞凋亡的影响并探讨其作用机制。方法将雄性Balb/c小鼠随机分为:正常组、模型组、美沙拉嗪组(5-ASA,200 mg/kg)、黄芩汤低、中、高剂量组(HQDL,2.275 g/kg;HQDM,4.55 g/kg;HQDH,9.1 g/kg),8只/组。各组自由饮食,除正常组自由饮用无菌水外,其余各组小鼠自由饮用3%DSS溶液,持续7d以建立UC模型。取结肠组织采用HE、AB-PAS和TUNEL染色分别观察结肠损伤和细胞凋亡情况,采用ELISA法检测炎症因子表达变化;采用Western blotting、免疫组化和qRT-PCR法分别检测肠道化学屏障、机械屏障、内质网应激等相关指标的蛋白或基因表达变化。结果与模型组相比,黄芩汤干预下的UC小鼠,DAI评分和宏观评分下降(P<0.01),TUNEL染色荧光强度下降(P<0.01)。促炎因子IL-6、TNF-α、IL-1β、IL-8表达减少(P<0.01),MUC2和TFF3的基因表达升高(P<0.05),Claudin-1、Occludin和E-cadherin的蛋白表达升高(P<0.05),GRP78、CHOP和Caspase-12的基因和蛋白表达下降(P<0.01)、PERK、eIF2α和IRE1α的磷酸化表达降低(P<0.05),Bcl-2/Bax蛋白表达比例升高(P<0.01)和Caspase-3的蛋白表达降低(P<0.01)。结论黄芩汤能够抑制UC小鼠的细胞凋亡反应并改善肠道屏障功能,其机制可能与PERK和IRE1α信号通路介导的内质网应激有关。 Objective To evaluate the therapeutic effect of Huangqin Decoction(HQD)on ulcerative colitis(UC)in mice and explore its mechanism.Methods Male Balb/c mice were randomly divided into normal control group,model group,mesalazine group(5-ASA,200 mg/kg),and low-,medium-and high-dose HQD groups(2.275,4.55 and 9.1 g/kg,respectively).With the exception of those in the normal control group,all the mice were exposed to 3%DSS solution in drinking water for 7 days to establish UC models.After treatment with the indicated drugs,the mice were assessed for colon injury and apoptosis using HE,AB-PAS and TUNEL staining,and the expression levels of inflammatory factors were detected with ELISA.Western blotting,immunohistochemistry and qRT-PCR were used to detect the changes in protein expressions associated with the intestinal chemical barrier,mechanical barrier and endoplasmic reticulum stress(ERS).Results HQD treatment significantly reduced DAI score and macro score of UC mice,decreased colonic epithelial cell apoptosis,lowered expressions of IL-6,TNF-α,IL-1βand IL-8,and enhanced the expressions of MUC2 and TFF3.HQD treatment also upregulated the protein expressions of claudin-1,occludin and E-cadherin,reduced the expressions of GRP78,CHOP,caspase-12 and caspase-3,decreased the phosphorylation levels of PERK,eIF2αand IRE1α,and increased the Bcl-2/Bax ratio in the colon tissues of UC mice.Conclusion HQD inhibits colonic epithelial cell apoptosis and improves intestinal barrier function in UC mice possibly by reducing ERS mediated by the PERK and IRE1αsignaling pathways.
作者 邱建国 邱一桐 李国荣 张林生 郑雪 姚泳江 王熙丹 黄海阳 张凤敏 苏冀彦 郑学宝 黄晓其 Jianguo QIU;Yitong QIU;Guorong LI;Linsheng ZHANG;Xue ZHENG;Yongjiang YAO;Xidan WANG;Haiyang HUANG;Fengmin ZHANG;Jiyan SU;Xuebao ZHENG;Xiaoqi HUANG(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Dongguan Hospital of Guangzhou University of Chinese Medicine,Dongguan 523000,China;Dongguan Institute of Guangzhou University of Chinese Medicine,Dongguan 523000,China;Foshan Maternal and Child Health Hospital,Foshan 528000,China)
出处 《南方医科大学学报》 CAS CSCD 北大核心 2024年第11期2172-2183,共12页 Journal of Southern Medical University
基金 国家自然科学基金(82274227) 广东省基础与应用基础研究基金(2022A1515140011,2021B1515140043,2022A1515010092,2021A1515220162)
关键词 溃疡性结肠炎 黄芩汤 内质网应激 细胞凋亡 ulcerative colitis Huangqin Decoction endoplasmic reticulum stress apoptosis
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