黄芩汤通过抑制TXNIP/NLRP3通路恢复溃疡性结肠炎大鼠免疫稳态并抑制结肠细胞凋亡

罗宁; 陈小露; 魏意霞; 谭朝晖; 方家祺; 颜景颖

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罗宁, 陈小露, 魏意霞, 谭朝晖, 方家祺, 颜景颖.黄芩汤通过抑制TXNIP/NLRP3通路恢复溃疡性结肠炎大鼠免疫稳态并抑制结肠细胞凋亡[J].湖南中医药大学学报,2026,46(4):688-696[点击复制]

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黄芩汤通过抑制TXNIP/NLRP3通路恢复溃疡性结肠炎大鼠免疫稳态并抑制结肠细胞凋亡

罗宁,陈小露,魏意霞,谭朝晖,方家祺,颜景颖

(北京中医药大学深圳医院(龙岗)药学部, 广东深圳 518172;深圳市龙岗区人民医院消化内科, 广东深圳 518172;北京中医药大学深圳医院(龙岗)肛肠科, 广东深圳 518172)

摘要:

目的研究黄芩汤对溃疡性结肠炎（UC）大鼠免疫调节及结肠细胞凋亡的影响，并基于硫氧还蛋白相互作用蛋白（TXNIP）/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)通路探讨黄芩汤的药理作用机制。方法将大鼠随机分为对照（Control）组和造模组，造模组采用肠内注射含有50%乙醇以及5%的2,4,6-三硝基苯磺酸的混合溶液法建立UC大鼠模型，造模完成后随机分为UC组、黄芩汤低剂量组（HQD-L组）、黄芩汤中剂量组（HQD-M组）、黄芩汤高剂量组（HQD-H组）、美沙拉嗪组，每组12只大鼠。HQD-L组、HQD-M组、HQD-H组分别给予5、10、20 g/kg黄芩汤灌胃，美沙拉嗪组给予270 mg/kg美沙拉嗪灌胃，Control组、UC组给予等量生理盐水灌胃。每组给药1次/d，连续21 d。末次给药结束后对大鼠疾病活动指数进行评分；流式细胞仪测定调节性T细胞（Treg）、辅助性T细胞（Th）17比例，并计算Treg/Th17比值；ELISA测定血清白细胞介素（IL）-1β、IL-4、IL-6、IL-10、干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β1水平和结肠组织超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）水平；HE染色观察结肠组织病理变化；TUNEL法检查结肠组织细胞凋亡率；RT-qPCR检测TXNIP、NLRP3 mRNA表达水平；Western blot检测TXNIP、NLRP3、半胱天冬酶-3(Caspase-3)、B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白（Bax）蛋白表达水平。结果与Control组比较，UC组的疾病活动指数评分，Th17比例、IL-1β、IL-6、IFN-γ、TNF-α、MDA水平，结肠组织细胞凋亡率，TXNIP和NLRP3 mRNA表达水平及TXNIP、NLRP3、Bax、Caspase-3蛋白表达水平均升高（P<0.05）;Treg比例、Treg/Th17比值、IL-4、IL-10、TGF-β1、SOD、GSH-Px、CAT水平及Bcl-2蛋白表达水平均降低（P<0.05）。与UC组比较，HQD-L组、HQD-M组、HQD-H组、美沙拉嗪组的疾病活动指数评分，Th17比例、IL-1β、IL-6、IFN-γ、TNF-α、MDA水平，结肠组织细胞凋亡率，TXNIP和NLRP3 mRNA表达水平及TXNIP、NLRP3、Bax、Caspase-3蛋白表达水平均降低（P<0.05）;Treg比例、Treg/Th17比值、IL-4、IL-10、TGF-β1、SOD、GSH-Px、CAT水平及Bcl-2蛋白表达水平均升高（P<0.05）。美沙拉嗪组与HQD-L组、HQD-M组比较，Th17比例、IL-1β、IL-6、IFN-γ、TNF-α、MDA水平，TXNIP和NLRP3 mRNA表达水平及蛋白表达水平均降低（P<0.05）；与HQD-H组比较上述指标升高（P<0.05）。美沙拉嗪组与HQD-L组、HQD-M组比较，Treg比例、Treg/Th17比值、IL-4、IL-10、TGF-β1、SOD、GSH-Px、CAT水平及Bcl-2蛋白表达水平均升高（P<0.05）；与HQD-H组比较上述指标降低（P<0.05）。结论黄芩汤能调节UC大鼠免疫平衡，抑制炎症反应和氧化损伤，抑制UC疾病进展，降低结肠组织细胞凋亡率，其机制可能与调节TXNIP/NLRP3通路有关。

DOI：10.3969/j.issn.1674-070X.2026.04.005

投稿时间：2025-12-18

基金项目:深圳市龙岗区科技创新专项资金医疗卫生科技计划项目(LGWJ2023-095);深圳市自然科学基金计划项目(JCYJ20250604185407010)

Huangqin Decoction restores immune homeostasis and inhibits colonic cell apoptosis in rats with ulcerative colitis by suppressing the TXNIP/NLRP3 pathway

LUO Ning, CHEN Xiaolu, WEI Yixia, TAN Zhaohui, FANG Jiaqi, YAN Jingying

(Department of Pharmacy, Shenzhen Hospital of Beijing University of Chinese Medicine (Longgang), Shenzhen, Guangdong 518172, China;Department of Gastroenterology, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong 518172, China;Department of Proctology, Shenzhen Hospital of Beijing University of Chinese Medicine (Longgang), Shenzhen, Guangdong 518172, China)

Abstract:

Objective To investigate the effects of Huangqin Decoction(HQD) on immune regulation and colonic cell apoptosis in rats with ulcerative colitis(UC), and to explore its pharmacological mechanism of action based on the thioredoxininteracting protein(TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) pathway. Methods Rats were randomly divided into control and model groups. A UC rat model was established in the model group by intracolonic injection of a mixed solution containing 50% ethanol and 5% 2,4,6-trinitrobenzene sulfonic acid. After successful modeling, the rats in the model group were randomly assigned to UC, HQD-L, HQD-M, HQD-H, and mesalazine groups, with 12 rats in each group. The HQD-L,HQD-M, and HQD-H groups received HQD by gavage at doses of 5, 10, and 20 g/kg, respectively. The mesalazine group received mesalazine by gavage at 270 mg/kg. The control and UC groups received equal volumes of normal saline by gavage. All groups were treated once daily for 21 consecutive days. After the final administration, disease activity index scores were assessed. The proportions of regulatory T cells(Treg) and T helper 17 cells(Th17) were determined by flow cytometry, and the Treg/Th17 ratio was calculated. ELISA was employed to measure the serum levels of interleukin(IL)-1β, IL-4, IL-6, IL-10, interferon(IFN)-γ, tumor necrosis factor(TNF)-α, and transforming growth factor(TGF)-β1, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px), and catalase(CAT) in colonic tissues. HE staining was used to observe the histopathological changes in colonic tissues. TUNEL was used to examine the apoptosis rate of colonic tissue cells. The mRNA expression levels of TXNIP and NLRP3 were tested by RT-qPCR. Protein expression levels of TXNIP, NLRP3, Caspase-3, B-cell lymphoma-2(Bcl-2),and Bcl-2-associated X protein(Bax) were determined by Western blot. Results Compared with the control group, the UC group showed increased disease activity index scores, higher Th17 proportion, elevated levels of IL-1β, IL-6, IFN-γ, TNF-α, and MDA,and increased apoptosis rate in colonic tissues; increased mRNA expression levels of TXNIP and NLRP3; and increased protein expression levels of TXNIP, NLRP3, Bax, and caspase-3(P<0.05). In contrast, the Treg proportion, Treg/Th17 ratio, levels of IL-4,IL-10, TGF-β1, SOD, GSH-Px, and CAT, and Bcl-2 protein expression levels were decreased(P<0.05). Compared with the UC group, the HQD-L, HQD-M, HQD-H, and mesalazine groups showed lower disease activity index scores; reduced Th17 proportion;decreased levels of IL-1β, IL-6, IFN-γ, TNF-α, and MDA; reduced apoptosis rate in colonic tissues; decreased mRNA expression levels of TXNIP and NLRP3; and decreased protein expression levels of TXNIP, NLRP3, Bax, and caspase-3(P<0.05). Meanwhile,the Treg proportion, Treg/Th17 ratio, levels of IL-4, IL-10, TGF-β1, SOD, GSH-Px, and CAT, and Bcl-2 protein expression were increased(P<0.05). Compared with the HQD-L and HQD-M groups, the mesalazine group showed reduced levels of Th17 proportion,IL-1β, IL-6, IFN-γ, TNF-α, and MDA, as well as decreased mRNA and protein expression levels of TXNIP and NLRP3(P<0.05);however, these parameters were elevated when compared with the HQD-H group(P<0.05). Compared with the HQD-L and HQD-M groups, the MSLZ group showed increased Treg proportions, Treg/Th17 ratios, and levels of IL-4, IL-10, TGF-β1, SOD, GSH-Px,and CAT, as well as increased Bcl-2 protein expression(P<0.05); compared with the HQD-H group, these parameters were decreased(P<0.05). Conclusion HQD can regulate immune balance in UC rats, inhibit inflammatory responses and oxidative damage,suppress disease progression, and reduce the apoptosis rate of colonic tissue cells. Its mechanism of action may be related to regulation of the TXNIP/NLRP3 pathway.

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