中草药

基于细胞自噬调控NLRP3/Caspase-1/GSDMD信号通路探讨五味子乙素减轻溃疡性结肠炎大鼠上皮细胞焦亡的作用机制

PDF下载

李欢 ¹,,² , 史孟华 ¹,,³, , 王志欣 ¹,,² , 杨青芸 ¹,,² , 郭海霞 ¹,,³, , 王杰 ⁴ , 张双喜 ¹,,³, , 安永康 ¹,,³, , 张相安 ¹,,³,

中草药 | 药理与临床 2026,57(16): 6401-6410

收起

中草药 |药理与临床 2026 , 57 (16) : 6401 -6410

基于细胞自噬调控NLRP3/Caspase-1/GSDMD信号通路探讨五味子乙素减轻溃疡性结肠炎大鼠上皮细胞焦亡的作用机制

全屏

李欢¹,,², 史孟华¹,,³,, 王志欣¹,,², 杨青芸¹,,², 郭海霞¹,,³,, 王杰⁴, 张双喜¹,,³,, 安永康¹,,³,, 张相安¹,,³,

作者信息

^1.河南中医药大学第一附属医院肛肠科, 河南郑州 450000

^2.河南中医药大学第一临床医学院, 河南郑州 450046

^3.河南中医药大学第一附属医院肛肠诊疗中心, 河南郑州 450000

^4.上海中医药大学, 上海 201203

^5.河南中医药大学第一附属医院肛肠科, 河南郑州 450000

^6.河南中医药大学第一附属医院肛肠诊疗中心, 河南郑州 450000

通讯作者:

安永康

作者简介:

李欢: 李欢,男,硕士研究生,研究方向为中医药防治肛肠病研究。E-mail:724359388@qq.com

Mechanism of schisandrin B in alleviating pyroptosis of epithelial cells in rats with ulcerative colitis based on regulation of NLRP3/Caspase-1/GSDMD signaling pathway by autophagy

Affiliations

出版时间: 2026-08-28 doi: 10.7501/j.issn.0253-2670.2026.16.015

文章导航

摘要

收起

目的研究五味子乙素（schisandrin B，Sch B）对2,4,6-三硝基苯磺酸（2,4,6-trinitrobenzenesulfonic acid solution，TNBS）诱导的大鼠溃疡性结肠炎（ulcerative colitis，UC）的治疗作用，探讨其通过调控细胞自噬相关蛋白及NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）/半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1，Caspase-1）/消皮素D（gasdermin D，GSDMD）信号通路减轻结肠上皮细胞焦亡的分子机制。方法 SD大鼠随机分为对照组、模型组、美沙拉嗪（100 mg/kg）组和Sch B低、中、高剂量（10、20、50 mg/kg）组，每组10只，雌雄各半。构建TNBS诱导的UC模型，给药干预14 d后，观察大鼠一般状态，检测疾病活动指数（disease activity index，DAI）评分、结肠长度及结肠黏膜损伤指数（colon mucosa damage index，CMDI）评分；苏木素-伊红（hematoxylin-eosin，HE）染色评估结肠组织病理损伤；ELISA检测血清中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）和IL-1β水平；免疫组化检测结肠组织自噬相关16样蛋白1（autophagy related protein 16 like protein 1，ATG16L1）和GSDMD蛋白表达；Western blotting检测结肠组织自噬相关蛋白[Beclin-1、微管相关蛋白轻链3B（microtubule-associated protein light chain 3B，LC3B）、ATG16L1、p62]及焦亡通路相关蛋白（NLRP3、Caspase-1、GSDMD）的表达。结果与模型组比较，Sch B显著改善UC大鼠体质量下降、便血等症状，降低DAI及CMDI评分（P＜0.05、0.01），增加结肠长度（P＜0.05、0.01），减轻结肠黏膜充血水肿、溃疡形成及炎症细胞浸润（P＜0.05、0.01），降低血清IL-6、TNF-α和IL-1β水平（P＜0.05、0.01），上调结肠组织Beclin-1蛋白表达并升高LC3-Ⅱ/Ⅰ值（P＜0.01），下调ATG16L1、p62、NLRP3、Caspase-1和GSDMD蛋白表达（P＜0.05、0.01）。结论 Sch B对TNBS诱导的UC大鼠具有显著治疗作用，其机制可能与调节细胞自噬流稳态、抑制NLRP3/Caspase-1/GSDMD信号通路介导的结肠上皮细胞焦亡、减少促炎因子释放以减轻肠道炎症反应相关，自噬流的正常化可能是Sch B抑制结肠上皮细胞焦亡的重要调控环节。

关键词

五味子乙素 / 溃疡性结肠炎 / 细胞焦亡 / 细胞自噬 / 炎症反应 / NLRP3/Caspase-1/GSDMD信号通路

Abstract

收起

Objective To investigate the therapeutic effect of schisandrin B (Sch B) on ulcerative colitis (UC) in rats induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS), and explore its molecular mechanism in alleviating pyroptosis of colonic epithelial cells by regulating autophagy-related proteins as well as NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/cysteine-aspartic protease-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway. Methods SD rats were randomly divided into control group, model group, mesalazine (100 mg/kg) group, Sch B low-, medium- and high-dose (10, 20, 50 mg/kg) groups, with 10 rats in each group, half male and half female. A TNBS-induced UC model was constructed, after 14 consecutive days of administration, the general conditions of rats were observed. The disease activity index (DAI) score, colon length and colon mucosa damage index (CMDI) score were detected. Histopathological injury of colonic tissue was evaluated by hematoxylin-eosin (HE) staining. Levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in serum were measured by ELISA. The expressions of autophagy related protein 16 like protein 1 (ATG16L1) and GSDMD proteins in colonic tissue were detected by immunohistochemistry. Western blotting was performed to detect the expressions of autophagy-related proteins (Beclin-1, microtubule-associated protein light chain 3B (LC3B), ATG16L1, p62) and pyroptosis pathway-related proteins (NLRP3, Caspase-1, GSDMD) in colonic tissue. Results Compared with model group, Sch B significantly ameliorated body weight loss, hematochezia and other symptoms in UC rats, reduced DAI and CMDI scores (P < 0.05, 0.01), increased colon length (P < 0.05, 0.01), alleviated colonic mucosal congestion, edema, ulcer formation and inflammatory cell infiltration (P < 0.05, 0.01), decreased levels of IL-6, TNF-α and IL-1β in serum (P < 0.05, 0.01), upregulated Beclin-1 protein expression and LC3-Ⅱ/Ⅰ ratio in colonic tissue (P < 0.01), and downregulated ATG16L1, p62, NLRP3, Caspase-1, GSDMD protein expressions (P < 0.05, 0.01). Conclusion Sch B exerts a remarkable therapeutic effect on TNBS-induced UC in rats. Its mechanism may be associated with maintaining autophagy flux homeostasis, inhibiting colonic epithelial cell pyroptosis mediated by NLRP3/Caspase-1/GSDMD signaling pathway, reducing the release of pro-inflammatory factors and thereby alleviating intestinal inflammatory response. Normalization of autophagy flux may be a key regulatory link for Sch B to inhibit colonic epithelial cell pyroptosis.

Key words

schisandrin B / ulcerative colitis / pyroptosis / autophagy / inflammatory response / NLRP3/Caspase-1/GSDMD signaling pathway

引用本文

李欢, 史孟华, 王志欣, 杨青芸, 郭海霞, 王杰, 张双喜, 安永康, 张相安. 基于细胞自噬调控NLRP3/Caspase-1/GSDMD信号通路探讨五味子乙素减轻溃疡性结肠炎大鼠上皮细胞焦亡的作用机制. 中草药, 2026 , 57 (16) : 6401 -6410 . DOI: 10.7501/j.issn.0253-2670.2026.16.015

LI Huan, SHI Menghua, WANG Zhixin, YANG Qingyun, GUO Haixia, WANG Jie, ZHANG Shuangxi, AN Yongkang, ZHANG Xiangan. Mechanism of schisandrin B in alleviating pyroptosis of epithelial cells in rats with ulcerative colitis based on regulation of NLRP3/Caspase-1/GSDMD signaling pathway by autophagy[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (16) : 6401 -6410 . DOI: 10.7501/j.issn.0253-2670.2026.16.015

基金

收起

国家自然科学基金面上项目
河南省科技研发计划联合基金资助项目
河南省科技攻关项目
河南省中医药科学研究专项

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

Bisgaard T H, Allin K H, Keefer L, et al. Depression and anxiety in inflammatory bowel disease: Epidemiology, mechanisms and treatment [J]. Nat Rev Gastroenterol Hepatol, 2022, 19(11): 717-726.

Park S H, Park S H. Personalized medicine in inflammatory bowel disease: Perspectives on Asia [J]. J Gastroenterol Hepatol, 2022, 37(8): 1434-1445.

Xu L, He B J, Sun Y X, et al. Incidence of inflammatory bowel disease in urban China: A nationwide population-based study [J]. Clin Gastroenterol Hepatol, 2023, 21(13): 3379-3386.e29.

Rieder F, Mukherjee P K, Massey W J, et al. Fibrosis in IBD: From pathogenesis to therapeutic targets [J]. Gut, 2024, 73(5): 854-866.

Mak J W Y, Ng S C. Epidemiology of fibrostenosing inflammatory bowel disease [J]. J Dig Dis, 2020, 21(6):332-335.

Latella G, Di Gregorio J, Flati V, et al. Mechanisms of initiation and progression of intestinal fibrosis in IBD [J]. Scand J Gastroenterol, 2015, 50(1): 53-65.

沈洪, 胡静怡, 朱磊, 等. 中医药治疗溃疡性结肠炎的研究现状、挑战与策略[J]. 南京中医药大学学报, 2025, 41(10):1267-1273.

岳诗棋, 张永宣, 王妍, 等. 中医药调控氨基酸代谢重编程治疗溃疡性结肠炎的研究进展[J]. 中草药, 2025, 56(24): 9233-9245.

刘继艳, 王冰, 李超宇, 等. 五味子非药用部位活性成分和药理作用研究进展[J]. 中草药, 2024, 55(9): 3179-3189.

马骏池, 赵晋彤, 高世勇, 等. 五味子乙素提纯工艺及药理作用研究进展[J]. 中国现代中药, 2022, 24(3): 533-541.

Foerster E G, Mukherjee T, Cabral-Fernandes L, et al. How autophagy controls the intestinal epithelial barrier [J]. Autophagy, 2022, 18(1): 86-103.

Xu Y, Shen J, Ran Z H. Emerging views of mitophagy in immunity and autoimmune diseases [J]. Autophagy, 2020, 16(1): 3-17.

Zhang D, Ge F, Ji J, et al. β-Sitosterol alleviates dextran sulfate sodium-induced experimental colitis via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis [J]. Front Pharmacol, 2023, 14: 1218477.

Ye Z, Li L Z, Li Y Z, et al. Tou Nong Powder obstructs ulcerative colitis through the regulation of NF-κB/ NLRP3/Caspase-1/GSDMD inflammasome pyroptotic pathway [J]. J Ethnopharmacol, 2023, 317: 116846.

陈玲玲, 陈熔杰. 五味子乙素对溃疡性结肠炎模型大鼠的干预及作用机制研究[J]. 中国药师, 2018, 21(11): 1941-1945.

Li W D, Liu Y, Wang Z, et al. Suppression of MAPK and NF-κB pathways by schisandrin B contributes to attenuation of DSS-induced mice model of inflammatory bowel disease [J]. Pharmazie, 2015, 70(9): 598.

洪晓娜, 蔡少卿, 孙祖凯. 胡黄连苷II调节Notch/Hes1信号通路对溃疡性结肠炎大鼠Th1/Th2细胞平衡的影响[J]. 中国老年学杂志, 2025, 45(24):6110-6114.

Murthy S N S, Cooper H S, Shim H, et al. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin [J]. Dig Dis Sci, 1993, 38(9): 1722-1734.

Mao J W, Tang H Y, Wang Y D. Influence of rosiglitazone on the expression of PPARγ, NF-κB, and TNF-α in rat model of ulcerative colitis [J]. Gastroenterol Res Pract, 2012, 2012: 845672.

刘丽君, 詹佳浩, 帅锦浩, 等. 栀子黄色素对葡聚糖硫酸钠诱导大鼠结肠炎的缓解作用及肠道菌群的影响[J]. 食品工业科技, 2025, 46(5): 344-354.

Wangchuk P, Yeshi K, Loukas A. Ulcerative colitis: Clinical biomarkers, therapeutic targets, and emerging treatments [J]. Trends Pharmacol Sci, 2024, 45(10): 892-903.

白文宇, 王厚恩, 王冰瑶, 等. 五味子化学成分及其药理作用研究进展[J]. 中成药, 2019, 41(9): 2177-2183.

戴国梁, 贡涛, 李豫, 等. 五味子乙素通过VEGF/ PI3K/Akt信号通路抑制人结肠癌细胞SW620的增殖和迁移[J]. 中国药学杂志, 2018, 53(14): 1186-1191.

Neurath M F, Artis D, Becker C. The intestinal barrier: A pivotal role in health, inflammation, and cancer [J]. Lancet Gastroenterol Hepatol, 2025, 10(6): 573-592.

Li X D, Wu X, Wang Q, et al. Sanguinarine ameliorates DSS induced ulcerative colitis by inhibiting NLRP3 inflammasome activation and modulating intestinal microbiota in C57BL/6 mice [J]. Phytomedicine, 2022, 104: 154321.

Xue J C, Yuan S, Hou X T, et al. Natural products modulate NLRP3 in ulcerative colitis [J]. Front Pharmacol, 2023, 14: 1265825.

Kong J R, Xiang Q Z, Ge W Y, et al. Network pharmacology mechanisms and experimental verification of licorice in the treatment of ulcerative colitis [J]. J Ethnopharmacol, 2024, 324:117691.

Larabi A, Barnich N, Nguyen H T T. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD [J]. Autophagy, 2020, 16(1): 38-51.

Mauduit A, Mas E, Solà-Tapias N, et al. Main genetic factors associated with inflammatory bowel diseases and their consequences on intestinal permeability: Involvement in gut inflammation [J]. J Gastroenterol, 2025, 60(11): 1323-1338.

Jie F M, Xiao S T, Qiao Y, et al. Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro [J]. J Ethnopharmacol, 2021, 264: 113243.

Qiao D, Liu X Y, Zhang Y L, et al. Jianpi-Qingchang Decoction alleviates ulcerative colitis by modulating endoplasmic reticulum stress-related autophagy in intestinal epithelial cells [J]. Biomed Pharmacother, 2023, 158: 114133.

Bisgaard T H, Allin K H, Keefer L, et al. Depression and anxiety in inflammatory bowel disease: Epidemiology, mechanisms and treatment [J]. Nat Rev Gastroenterol Hepatol, 2022, 19(11): 717-726.
Park S H, Park S H. Personalized medicine in inflammatory bowel disease: Perspectives on Asia [J]. J Gastroenterol Hepatol, 2022, 37(8): 1434-1445.
Xu L, He B J, Sun Y X, et al. Incidence of inflammatory bowel disease in urban China: A nationwide population-based study [J]. Clin Gastroenterol Hepatol, 2023, 21(13): 3379-3386.e29.
Rieder F, Mukherjee P K, Massey W J, et al. Fibrosis in IBD: From pathogenesis to therapeutic targets [J]. Gut, 2024, 73(5): 854-866.
Mak J W Y, Ng S C. Epidemiology of fibrostenosing inflammatory bowel disease [J]. J Dig Dis, 2020, 21(6):332-335.
Latella G, Di Gregorio J, Flati V, et al. Mechanisms of initiation and progression of intestinal fibrosis in IBD [J]. Scand J Gastroenterol, 2015, 50(1): 53-65.
沈洪, 胡静怡, 朱磊, 等. 中医药治疗溃疡性结肠炎的研究现状、挑战与策略[J]. 南京中医药大学学报, 2025, 41(10):1267-1273.
岳诗棋, 张永宣, 王妍, 等. 中医药调控氨基酸代谢重编程治疗溃疡性结肠炎的研究进展[J]. 中草药, 2025, 56(24): 9233-9245.
刘继艳, 王冰, 李超宇, 等. 五味子非药用部位活性成分和药理作用研究进展[J]. 中草药, 2024, 55(9): 3179-3189.
马骏池, 赵晋彤, 高世勇, 等. 五味子乙素提纯工艺及药理作用研究进展[J]. 中国现代中药, 2022, 24(3): 533-541.
Foerster E G, Mukherjee T, Cabral-Fernandes L, et al. How autophagy controls the intestinal epithelial barrier [J]. Autophagy, 2022, 18(1): 86-103.
Xu Y, Shen J, Ran Z H. Emerging views of mitophagy in immunity and autoimmune diseases [J]. Autophagy, 2020, 16(1): 3-17.
Zhang D, Ge F, Ji J, et al. β-Sitosterol alleviates dextran sulfate sodium-induced experimental colitis via inhibition of NLRP3/Caspase-1/GSDMD-mediated pyroptosis [J]. Front Pharmacol, 2023, 14: 1218477.
Ye Z, Li L Z, Li Y Z, et al. Tou Nong Powder obstructs ulcerative colitis through the regulation of NF-κB/ NLRP3/Caspase-1/GSDMD inflammasome pyroptotic pathway [J]. J Ethnopharmacol, 2023, 317: 116846.
陈玲玲, 陈熔杰. 五味子乙素对溃疡性结肠炎模型大鼠的干预及作用机制研究[J]. 中国药师, 2018, 21(11): 1941-1945.
Li W D, Liu Y, Wang Z, et al. Suppression of MAPK and NF-κB pathways by schisandrin B contributes to attenuation of DSS-induced mice model of inflammatory bowel disease [J]. Pharmazie, 2015, 70(9): 598.
洪晓娜, 蔡少卿, 孙祖凯. 胡黄连苷II调节Notch/Hes1信号通路对溃疡性结肠炎大鼠Th1/Th2细胞平衡的影响[J]. 中国老年学杂志, 2025, 45(24):6110-6114.
Murthy S N S, Cooper H S, Shim H, et al. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin [J]. Dig Dis Sci, 1993, 38(9): 1722-1734.
Mao J W, Tang H Y, Wang Y D. Influence of rosiglitazone on the expression of PPARγ, NF-κB, and TNF-α in rat model of ulcerative colitis [J]. Gastroenterol Res Pract, 2012, 2012: 845672.
刘丽君, 詹佳浩, 帅锦浩, 等. 栀子黄色素对葡聚糖硫酸钠诱导大鼠结肠炎的缓解作用及肠道菌群的影响[J]. 食品工业科技, 2025, 46(5): 344-354.
Wangchuk P, Yeshi K, Loukas A. Ulcerative colitis: Clinical biomarkers, therapeutic targets, and emerging treatments [J]. Trends Pharmacol Sci, 2024, 45(10): 892-903.
白文宇, 王厚恩, 王冰瑶, 等. 五味子化学成分及其药理作用研究进展[J]. 中成药, 2019, 41(9): 2177-2183.
戴国梁, 贡涛, 李豫, 等. 五味子乙素通过VEGF/ PI3K/Akt信号通路抑制人结肠癌细胞SW620的增殖和迁移[J]. 中国药学杂志, 2018, 53(14): 1186-1191.
Neurath M F, Artis D, Becker C. The intestinal barrier: A pivotal role in health, inflammation, and cancer [J]. Lancet Gastroenterol Hepatol, 2025, 10(6): 573-592.
Li X D, Wu X, Wang Q, et al. Sanguinarine ameliorates DSS induced ulcerative colitis by inhibiting NLRP3 inflammasome activation and modulating intestinal microbiota in C57BL/6 mice [J]. Phytomedicine, 2022, 104: 154321.
Xue J C, Yuan S, Hou X T, et al. Natural products modulate NLRP3 in ulcerative colitis [J]. Front Pharmacol, 2023, 14: 1265825.
Kong J R, Xiang Q Z, Ge W Y, et al. Network pharmacology mechanisms and experimental verification of licorice in the treatment of ulcerative colitis [J]. J Ethnopharmacol, 2024, 324:117691.
Larabi A, Barnich N, Nguyen H T T. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD [J]. Autophagy, 2020, 16(1): 38-51.
Mauduit A, Mas E, Solà-Tapias N, et al. Main genetic factors associated with inflammatory bowel diseases and their consequences on intestinal permeability: Involvement in gut inflammation [J]. J Gastroenterol, 2025, 60(11): 1323-1338.
Jie F M, Xiao S T, Qiao Y, et al. Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro [J]. J Ethnopharmacol, 2021, 264: 113243.
Qiao D, Liu X Y, Zhang Y L, et al. Jianpi-Qingchang Decoction alleviates ulcerative colitis by modulating endoplasmic reticulum stress-related autophagy in intestinal epithelial cells [J]. Biomed Pharmacother, 2023, 158: 114133.

2026年第57卷第16期

PDF下载

109

引用本文

BibTeX

文章信息

doi: 10.7501/j.issn.0253-2670.2026.16.015

接收时间：2026-01-27
首发时间：2026-10-22
出版时间：2026-08-28

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2026-01-27

基金

国家自然科学基金面上项目

河南省科技研发计划联合基金资助项目

河南省科技攻关项目

河南省中医药科学研究专项

作者信息

^1.河南中医药大学第一附属医院肛肠科, 河南郑州 450000

^2.河南中医药大学第一临床医学院, 河南郑州 450046

^3.河南中医药大学第一附属医院肛肠诊疗中心, 河南郑州 450000

^4.上海中医药大学, 上海 201203

^5.河南中医药大学第一附属医院肛肠科, 河南郑州 450000

^6.河南中医药大学第一附属医院肛肠诊疗中心, 河南郑州 450000

通讯作者:

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/zcy/CN/10.7501/j.issn.0253-2670.2026.16.015

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

关闭全屏

BibTeX
EndNote
RefWorks
TxT