Qiu J, Qiu Y, Li G, Zhang L, Zheng X, Yao Y, Wang X, Huang H, Zhang F, Su J, Zheng X, Huang X
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Nov 20;44(11):2172-2183. doi: 10.12122/j.issn.1673-4254.2024.11.14.
To evaluate the therapeutic effect of Decoction (HQD) on ulcerative colitis (UC) in mice and explore its mechanism.
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).
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.
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.
评价化癖汤（HQD）对小鼠溃疡性结肠炎（UC）的治疗作用并探讨其作用机制。
将雄性Balb/c小鼠随机分为正常对照组、模型组、美沙拉嗪组（5-氨基水杨酸，200 mg/kg）以及低、中、高剂量HQD组（分别为2.275、4.55和9.1 g/kg）。除正常对照组小鼠外，其余小鼠饮用含3%葡聚糖硫酸钠（DSS）溶液的水7天以建立UC模型。用指定药物治疗后，采用苏木精-伊红（HE）、阿尔新蓝-过碘酸雪夫（AB-PAS）和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色评估小鼠结肠损伤和细胞凋亡情况，并用酶联免疫吸附测定（ELISA）检测炎症因子的表达水平。采用蛋白质免疫印迹法、免疫组织化学法和实时荧光定量聚合酶链反应（qRT-PCR）检测与肠道化学屏障、机械屏障和内质网应激（ERS）相关的蛋白质表达变化。
HQD治疗显著降低了UC小鼠的疾病活动指数（DAI）评分和大体评分，减少了结肠上皮细胞凋亡，降低了白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β和白细胞介素-8的表达，并增强了黏蛋白2（MUC2）和三叶因子3（TFF3）的表达。HQD治疗还上调了闭合蛋白-1、闭锁蛋白和E-钙黏蛋白的蛋白表达，降低了葡萄糖调节蛋白78（GRP78）、Caspase-12、Caspase-3的表达，降低了蛋白激酶样内质网激酶（PERK）、真核细胞起始因子2α（eIF2α）和肌醇需求酶1α（IRE1α）的磷酸化水平，并提高了UC小鼠结肠组织中Bcl-2/Bax比值。
HQD可能通过减少PERK和IRE1α信号通路介导的ERS来抑制UC小鼠结肠上皮细胞凋亡并改善肠道屏障功能。
