中华中医药学刊

雷公藤甲素通过Integrin介导的细胞外基质重塑对博来霉素诱导肺纤维化小鼠的保护作用

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陈宏 ¹ , 张宁 ² , 张伟 ¹ , 李可心 ² , 于佳琪 ² , 齐鑫 ²

中华中医药学刊 | 博士导师新论 2026,44(7): 8-12

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中华中医药学刊 |博士导师新论 2026 , 44 (7) : 8 -12

雷公藤甲素通过Integrin介导的细胞外基质重塑对博来霉素诱导肺纤维化小鼠的保护作用

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陈宏¹, 张宁², 张伟¹, 李可心², 于佳琪², 齐鑫²

作者信息

^1.黑龙江中医药大学附属第一医院，黑龙江　哈尔滨　150040

^2.黑龙江中医药大学，黑龙江　哈尔滨　150040

作者简介:

陈宏（1977-），男，黑龙江哈尔滨人，主任医师，博士研究生导师，博士，研究方向：中医药防治小儿肺系疾病与心肝系统疾病。

Analysis on Protective Effect of Triptolide on Bleomycin-induced Pulmonary Fibrosis in Mice Through Integrin-mediated Extracellular Matrix Remodeling

Hong CHEN¹, Ning ZHANG², Wei ZHANG¹, Kexin LI², Jiaqi YU², Xin QI²

Affiliations

^1.The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang, China

^2.Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang, China

出版时间: 2026-07-10 doi: 10.13193/j.issn.1673-7717.2026.07.002

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摘要

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目的

探讨和分析雷公藤甲素（TPL）通过整合素（Integrin）介导的细胞外基质重塑对博来霉素（BLM）诱导肺纤维化小鼠的保护作用。

方法

将60只C57BL/6雄性小鼠作为研究样本并进行组别划分，即对照组、模型组、地塞米松组（DXM组）、TPL低剂量组及TPL高剂量组5组，每组12只。进行腹主动脉全血血气分析，记录氧分压（PO₂）和血氧饱和度（SO₂），应用HE染色进行肺病理组织学观察，进而确定各组小鼠氧化指标超氧化物歧化酶（SOD）、丙二醛（MDA）等的含量，通过细胞热迁移实验（CESTA）、表面等离子共振实验（SPR）确证雷公藤甲素与整合素-β1（ITG-β1）相互作用，以蛋白免疫印迹法（Western blot）确定ITG-β1、转化生长因子-β1（TGF-β1）和Smad3蛋白相对表达水平。

结果

TPL处理组和DXM组小鼠肺组织完整性较好，且两组的肺间质扩张减轻；同时，观察到两组小鼠肺泡之间缺失与融合得到修复，样本未伴有明显的间质炎性浸润，纤维增生得以有效缓解。与对照组比较，模型组小鼠PO₂、SO₂、SOD和谷胱甘肽过氧化物酶（GSH-Px）均显著下降，MDA含量明显升高（P<0.01）；与模型组比较，DXM组、TPL低剂量组和TPL高剂量组PO₂、SO₂、SOD和GSH-Px的水平明显升高，MDA含量明显下降（P<0.05）；与TPL低剂量组比较，TPL高剂量组作用效果更明显，PO₂、SOD和GSH-Px的水平升高更明显（P<0.05）。CESTA和SPR实验研究发现，雷公藤甲素与ITG-β1具有相互作用，因此推测是抗肺纤维化作用靶点。与对照组比较，模型组小鼠肺组织中ITG-β1、TGF-β1、Smad3的蛋白表达水平均升高（P<0.01）；DXM组、TPL低和高剂量组小鼠肺组织中ITG-β1、TGF-β1、Smad3的蛋白表达水平均低于模型组（P<0.05），且与DXM组、TPL低剂量组比较，TPL高剂量组小鼠肺组织中ITG-β1、TGF-β1、Smad3的蛋白表达水平均降低（P<0.05）。

结论

雷公藤甲素可通过整合素介导的细胞外基质重塑对博来霉素诱导肺纤维化小鼠起到保护作用，整合素引起的肺纤维化相关变化蛋白可作为雷公藤甲素治疗肺纤维化的靶点。

关键词

雷公藤甲素 / 整合素 / 细胞外基质重塑 / 肺纤维化 / 保护作用

Abstract

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Objective

To investigate and analyze the protective effect of triptolide (TPL) on bleomycin (BLM)-induced pulmonary fibrosis in mice induced by integrin-mediated extracellular matrix remodeling.

Methods

Sixty male C57BL/6 mice were randomly divided into control group, model group, dexamethasone group (DXM group), TPL low and high dose groups, with 12 mice in each group. Blood gas analysis was performed in whole blood of abdominal aorta, oxygen partial pressure (PO₂) and blood oxygen saturation (SO₂) were recorded, the pulmonary histology was observed by HE staining, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in mice sample in each group were detected. The interaction between triptolide and integrin β1 (ITG-β1) was confirmed by cell thermal migration assay (CESTA) and surface plasmonresonance assay (SPR), and the relative expression levels of ITG-β1, transforming growth factor-β1 (TGF-β1) and Smad3 were detected by Western blot.

Results

The lung tissue integrity of mice in TPL low and high dose groups and DXM group was better, and the interstitial expansion of the lungs was reduced in these groups. At the same time, it was observed that the loss and fusion between the alveoli of the mice in TPL groups and DXM group were repaired, and the samples did not show significant interstitial inflammatory infiltration, effectively alleviating fibrosis. Compared with those in the control group, the levels of PO₂, SO₂, SOD and GSH-Px in the model group were significantly decreased, and MDA content was significantly increased (P<0.01). Compared with those in the model group, the levels of PO₂, SO₂, SOD and GSH-Px in the DXM group, TPL low and high dose groups were significantly increased, while the content of MDA was significantly decreased (P<0.05). Compared with those in the TPL low dose group, the effect of TPL high dose group was more obvious, and the levels of PO₂, SOD and GSH-Px were increased more significantly (P<0.05). The results of CESTA and SPR experiments indicated that triptolide interacted with ITG-β1 and was a possible anti-pulmonary fibrosis target. Compared with those of the control group, the protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of the model group were increased (P<0.01). The protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of mice in the DXM group, TPL low and high dose groups were lower than those in the model group (P<0.05), and compared with those in the DXM group and TPL low dose group, the protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of mice in the TPL high dose group were decreased (P<0.05).

Conclusion

TPL can protect pulmonary fibrosis induced by bleomycin through extracellular matrix remodeling mediated by integrin, and the fibrosis-related change protein induced by integrin can be used as the target of TPL in the treatment of pulmonary fibrosis.

Key words

triptolide / integrin / extracellular matrix remodeling / pulmonary fibrosis / protective effect

引用本文

陈宏, 张宁, 张伟, 李可心, 于佳琪, 齐鑫. 雷公藤甲素通过Integrin介导的细胞外基质重塑对博来霉素诱导肺纤维化小鼠的保护作用. 中华中医药学刊, 2026 , 44 (7) : 8 -12 . DOI: 10.13193/j.issn.1673-7717.2026.07.002

Hong CHEN, Ning ZHANG, Wei ZHANG, Kexin LI, Jiaqi YU, Xin QI. Analysis on Protective Effect of Triptolide on Bleomycin-induced Pulmonary Fibrosis in Mice Through Integrin-mediated Extracellular Matrix Remodeling[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (7) : 8 -12 . DOI: 10.13193/j.issn.1673-7717.2026.07.002

基金

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中国博士后科学基金第13批特别项目(2020T130178)
黑龙江省自然科学基金项目(LH2023H074)
黑龙江省卫生健康委员会项目(20230202040115)

参考文献

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文献

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参考文献引证文献

排序方式：

[1]

李雅馨, 丁露, 杨映映, 等. 基于数据挖掘和网络药理学探讨中药复方治疗特发性肺纤维化的组方规律和潜在机制[J]. 中国老年学杂志, 2022, 42(9): 2119-2124.

[2]

李红梅, 张旭辉, 武妍琳, 等. TGF-β1/Smad信号通路在肺纤维化中的作用及中医药调控研究进展[J]. 中药药理与临床, 2024, 40(1): 123-128.

[3]

陈中沛, 李洁, 陈阳, 等. 培元通闭散结中药治疗新型冠状病毒肺炎恢复期肺纤维化的临床研究[J]. 世界科学技术-中医药现代化, 2023, 25(1): 380-386.

[4]

KAWAMI M, OJIMA T, YUMOTO R, et al. Role of integrin α2 in methotrexate-induced epithelial-mesenchymal transition in alveolar epithelial A549 cells[J]. Toxicol Res, 2022, 38(4): 449-458.

[5]

刘喜红, 杜晓丹, 范孟杨, 等. miR-328-3p-Akt/mTOR轴在雷公藤甲素抑制脑胶质瘤细胞生长中的作用及机制研究[J]. 中国实验动物学报, 2023, 31(6): 697-705.

[6]

李世杰, 张诗雨, 孙阳, 等. 雷公藤甲素对ox-LDL诱发的血管内皮细胞炎症反应的抑制作用及机制研究[J]. 世界科学技术-中医药现代化, 2023, 25(4): 1341-1349.

[7]

张艺, 郭芬. 雷公藤甲素联合吉非替尼对EGFR突变NSCLC细胞的协同效应分析[J]. 中国药房, 2023, 34(18): 2219-2225.

[8]

李建生, 李素云. 肺痿肺痹与肺纤维化[J]. 中医杂志, 2003, 44(11): 878-879.

[9]

RITZENTHALER J D, ZHANG M, TORRES-GONZALEZ E, et al. The integrin inhibitor cilengitide and bleomycin-induced pulmonary fibrosis: cilengitide and bleomycin-induced pulmonary fibrosis[J]. Lung, 2020, 198(6): 947-955.

[10]

NANRI Y, NUNOMURA S, TERASAKI Y, et al. Cross-talk between transforming growth factor-β and periostin can be targeted for pulmonary fibrosis[J]. Am J Respir Cell Mol Biol, 2020, 62(2): 204-216.

[11]

张彩霞, 王伟艳, 李会芳, 等. miR-20a通过ATG16L1影响细胞自噬并参与调节雷公藤甲素肝毒性[J]. 中草药, 2023, 54(13): 4214-4223.

[12]

周平安, 杨效华. 肺间质纤维化的中医认识与治疗[J]. 北京中医药大学学报, 2000, 23(2): 48-50.

[13]

王承德, 沈丕安, 胡荫奇. 实用中医风湿病学[M]. 2版. 北京: 人民卫生出版社, 2009: 789-792.

[14]

国家中医药管理局《中华本草》编委会. 中华本草-1[M]. 上海: 上海科学技术出版社, 1999: 2136-2138.

[15]

梁晓, 李昂昂, 彭勍, 等. LPS诱导的小鼠急性肺损伤后肺纤维化模型构建与机制研究[J]. 中国实验动物学报, 2025, 33(6): 848-857.

[16]

李乔, 王苗风, 田宇, 等. 一种改良的博来霉素诱导的肺纤维化模型造模方法[J]. 空军军医大学学报, 2024, 45(4): 425-429.

[17]

赵琰, 韩雯雯, 赵琳, 等. ICU机械通气患者呼吸机相关性肺炎的危险因素及WISP1/TLR4/整合素β5通路基因变化[J]. 中华医院感染学杂志, 2023, 33(23): 3557-3561.

[18]

VILLAS BOAS C W, LO W, HUYNH T, et al. PET/CT imaging of avb6 integrin to monitor radiation-induced pulmonary fibrosis[J]. Nucl Med Biol, 2023, 126: 108434.

[19]

张海龙, 王露, 郭雯, 等. 抗纤缓急方治疗特发性肺纤维化急性加重患者多中心随机对照研究[J]. 中国中西医结合杂志, 2024, 44(2): 163-168.

[20]

ZHANG Y W, ZHU L H, HONG J S, et al. Extracellular matrix of early pulmonary fibrosis modifies the polarization of alveolar macrophage[J]. Int Immunopharmacol, 2022, 111: 109179.

[21]

刘晋芳, 周儒奎, 高艳, 等. 博莱霉素在恶性肿瘤中应用的研究进展[J]. 山西中医药大学学报, 2021, 22(1): 75-79.

[22]

王搏, 宋庆华, 唐会猛, 等. 博来霉素诱导的肺纤维化动物模型研究进展[J]. 中国实验动物学报, 2023, 31(12): 1617-1628.

[23]

丁香, 刘健, 陈晓露, 等. 雷公藤甲素通过miR-23a-3p/PTEN/PI3K/AKT/mTOR改善强直性脊柱炎滑膜成纤维细胞作用机制[J]. 中华中医药杂志, 2023, 38(12): 6024-6029.

[24]

檀丽丽, 黄巍, 杨子璇, 等. 特发性肺纤维化动物模型的研究进展[J]. 中国实验动物学报, 2025, 33(5): 756-769.

[25]

卫博凯, 胡静. 基于中医传承辅助平台与网络药理学探析中药干预新型冠状病毒感染后遗症肺纤维化的作用机制[J]. 中草药, 2024, 55(1): 190-204.

[26]

SIME P, JENKINS G. Goldilocks and the three trials: clinical trials targeting the α_vβ₆ integrin in idiopathic pulmonary fibrosis[J]. Am J Respir Crit Care Med, 2022, 206(9): 1062-1063.

[27]

徐义峰, 柯诗文, 李可可, 等. 氧化应激和免疫浸润在特发性肺纤维化中的作用及中药防治研究[J]. 中国免疫学杂志, 2024, 40(10): 2108-2115.

[28]

KIM J W, JEONG M H, YU H T, et al. Fibrinogen on extracellular vesicles derived from polyhexamethylene guanidine phosphate-exposed mice induces inflammatory effects via integrin β[J]. Ecotoxicol Environ Saf, 2023, 252: 114600.

[29]

MEI S, TANG R, HU Y, et al. Integrin β3 mediates sepsis and mechanical ventilation-associated pulmonary fibrosis through glyco-metabolic reprogramming[J]. Lab Invest, 2023, 103(1): 100021.

2026年第44卷第7期

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doi: 10.13193/j.issn.1673-7717.2026.07.002

首发时间：2026-10-20
出版时间：2026-07-10

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基金

中国博士后科学基金第13批特别项目(2020T130178)

黑龙江省自然科学基金项目(LH2023H074)

黑龙江省卫生健康委员会项目(20230202040115)

作者信息

^1.黑龙江中医药大学附属第一医院，黑龙江　哈尔滨　150040

^2.黑龙江中医药大学，黑龙江　哈尔滨　150040

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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

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