[黄芩汤通过降低内质网应激减轻小鼠溃疡性结肠炎]。

J Qiu, Y Qiu, G Li, L Zhang, X Zheng, Y Yao, X Wang, H Huang, F Zhang, J Su, X Zheng, X Huang
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引用次数: 0

摘要

目的:评价黄芩汤对小鼠溃疡性结肠炎的治疗作用,并探讨其作用机制。方法:将雄性Balb/c小鼠随机分为正常对照组、模型组、美沙嗪组(5-ASA, 200 mg/kg)和HQD低、中、高剂量组(分别为2.275、4.55、9.1 g/kg)。除正常对照组外,其余小鼠均在饮用水中添加3% DSS溶液,连续7 d建立UC模型。给药后,采用HE、AB-PAS、TUNEL染色检测小鼠结肠损伤及凋亡情况,ELISA检测炎症因子表达水平。采用Western blotting、免疫组织化学和qRT-PCR检测肠道化学屏障、机械屏障和内质网应激(endoplasmic reticulum stress, ERS)相关蛋白的表达变化。结果:HQD治疗显著降低UC小鼠DAI评分和宏观评分,减少结肠上皮细胞凋亡,降低IL-6、TNF-α、IL-1β、IL-8表达,增强MUC2、TFF3表达。HQD还上调了UC小鼠结肠组织中claudin-1、occludin和E-cadherin的蛋白表达,降低了GRP78、CHOP、caspase-12和caspase-3的表达,降低了PERK、eIF2α和IRE1α的磷酸化水平,增加了Bcl-2/Bax比值。结论:HQD可能通过降低PERK和IRE1α信号通路介导的ERS,抑制UC小鼠结肠上皮细胞凋亡,改善肠道屏障功能。
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[Huangqin Decoction alleviates ulcerative colitis in mice by reducing endoplasmic reticulum stress].

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-1β and 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, eIF2α and 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 IRE1α signaling pathways.

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来源期刊
南方医科大学学报杂志
南方医科大学学报杂志 Medicine-Medicine (all)
CiteScore
1.50
自引率
0.00%
发文量
208
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