中华中医药学刊

基于TIPE2/TLR4-NF-κB通路探讨大黄素对肝内胆汁淤积大鼠的保护作用

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刘怡静 , 姚恒潘 , 李素丽 , 周方

中华中医药学刊 | 省级项目平台 2026,44(7): 246-251

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中华中医药学刊 |省级项目平台 2026 , 44 (7) : 246 -251

基于TIPE2/TLR4-NF-κB通路探讨大黄素对肝内胆汁淤积大鼠的保护作用

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刘怡静（1996-），女，河南三门峡人，硕士在读，研究方向：儿童肝脏疾病的中西医诊疗。

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刘怡静（1996-），女，河南三门峡人，硕士在读，研究方向：儿童肝脏疾病的中西医诊疗。

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刘怡静, 姚恒潘, 李素丽, 周方

作者信息

郑州大学附属儿童医院，河南省儿童医院郑州儿童医院，河南　郑州　450053

通讯作者:

周方（1978-），女，河南郑州人，主任医师，硕士研究生导师，硕士，研究方向：儿童消化系统疾病的中西医诊疗。E-mail：zf78@163.com。

作者简介:

刘怡静（1996-），女，河南三门峡人，硕士在读，研究方向：儿童肝脏疾病的中西医诊疗。

Discussion on Protective Effect of Emodin on Intrahepatic Cholestasis in Rats Based on TIPE2/TLR4-NF-κB Pathway

Yijing LIU, Hengpan YAO, Suli LI, Fang ZHOU

Affiliations

Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital, Zhengzhou 450053, Henan, China

出版时间: 2026-07-10 doi: 10.13193/j.issn.1673-7717.2026.07.045

文章导航

摘要

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目的

探讨大黄素对肝内胆汁淤积大鼠的保护作用及机制。

方法

将40只SD大鼠随机分为正常对照组、模型组、模型+大黄素组和正常+大黄素组，模型+大黄素组和正常+大黄素组给予大黄素40 mg·kg^-1·d^-1灌胃7 d，正常组及模型组给予羧甲基纤维素钠处理，于实验第5天给药4 h后，模型组和模型+大黄素组50 mg·kg^-1·d^-1给予α-萘异硫氰酸酯（alpha-naphthylisothiocyanate，ANIT）灌胃1次建立肝内胆汁淤积模型，其余两组予以橄榄油对照处理，建模后48 h处死动物，收集标本。HE染色观察肝脏病理改变；采用比色定量法检测各组实验动物血清丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）、γ-谷氨酰转移酶（gamma-glutamyl transferase，GGT）、血清总胆红素（total bilirubin，TBiL）、直接胆红素（direct bilirubin，DBiL）和总胆汁酸（total bile acid，TBA）水平；采用酶联免疫吸附试验（enzyme linked immunosorbent assay，ELISA）法检测肝脏组织丙二醛（malondialdehyde，MDA）、髓过氧化物酶（myeloperoxidase，MPO）、白细胞介素-1β（interleukin-1β，IL-1β）、肿瘤坏死因子-α（tumor necrosis factor，TNF-α）、白细胞介素-6（interleukin-6，IL-6）含量；实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction，qRT-PCR）检测单个核细胞肿瘤坏死因子-α诱导蛋白8样分子2（tumor necrosis factor-α-induced protein8-like2，TIPE2）及肝组织Toll样受体4（Toll-like receptor 4，TLR4）、核因子-κB（nuclear factor kappa B，NF-κB）mRNA表达；蛋白质印迹法（western blot，WB）检测肝组织TLR4、NF-κB和TIPE2蛋白表达。

结果

与正常对照组比较，模型组血清ALT、AST、GGT、TBiL、DBiL、TBA浓度及肝组织MDA、MPO、TNF-α、IL-6、IL-1β含量明显升高（P<0.01）；TIPE2 mRNA及蛋白水平表达下调（P<0.01），TLR4及NF-κB表达均升高（P<0.01）。与模型组相比，给予大黄素治疗后显著降低血清ALT、AST、GGT、TBiL、DBiL、TBA浓度及肝组织MDA、MPO、TNF-α、IL-6、IL-1β含量（P<0.01）；TIPE2 mRNA及蛋白表达均升高（P<0.01），下调TLR4及NF-κB表达（P<0.05，P<0.01）。

结论

大黄素可通过上调TIPE2的表达，抑制TLR4-NF-κB信号通路过度激活，进而抑制氧化应激及炎症反应，减轻胆汁淤积，发挥其保护作用。

关键词

大黄素 / 胆汁淤积 / 肿瘤坏死因子-α诱导蛋白8样分子2 / Toll样受体4 / 核因子-κB

Abstract

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Objective

Intrahepatic cholestasis is a common pathological condition of several types of liver disorders. In this study, it aimed to investigate the hepatoprotective effect of emodin against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) in rats.

Methods

Forty SD rats were randomly divided into control group, model group, emodin group with ANIT treatment and emodin group without ANIT treatment. Emodin group with and without ANIT treatment groups were intragastrically administrated emodin (40 mg·kg^-1·d^-1) for 7 days, and the control group and the model group were fed by sodium carboxymethylcellulose. On the 5th day after administration and fasting 4 h, the model group and the emodin group with ANIT treatment were given ANIT (50 mg·kg^-1·d^-1) to establish the intrahepatic cholestasis model, and the other two groups were fed by olive oil. At 48 h after the model establishment, the specimens were collected. The liver histopathological changes were observed by hematoxylin-eosin (HE). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBiL), direct bilirubin (DBiL) and total bile acid (TBA) in serum were determined by colorimetric quantitative method. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and interleukin-1β(IL-1β) of liver tissue were measured by ELISA. Quantitative fluorescent PCR was used to detect the expression levels of tumor necrosis factor-α-induced protein 8-like 2 (TIPE2), Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) mRNA. Western blot was used to evaluate the changes in the protein levels of TIPE2, TLR4 and NF-κB.

Results

Compared with those in the control group, the concentrations of ALT, AST, GGT, TBiL, DBiL and TBA, the contents of MDA, MPO, TNF-α, IL-6 and IL-1β were significantly increased in the model group (P<0.01). The mRNA and protein expressions of TIPE2 were down-regulated (P<0.01), while the expressions of TLR4 and NF-κB were increased (P<0.01). Compared with the model group, emodin treatment could reduce the levels of ALT, AST, GGT, TBiL, DBiL and TBA (P<0.01), decrease the concentrations of MDA, MPO, TNF-α, IL-6 and IL-1β(P<0.01), increase the expression of TIPE2 (P<0.01), meanwhile significantly inhibit the expressions of TLR4 and NF-κB (P<0.05, P<0.01).

Conclusion

Emodin has a protective effect against intrahepatic cholestasis in the rats through up-regulating the expression of TIPE2 and inhibition of the TLR4/NF-κB pathway.

Key words

emodin / cholestasis / TIPE2 / TLR4 / NF-κB

引用本文

刘怡静, 姚恒潘, 李素丽, 周方. 基于TIPE2/TLR4-NF-κB通路探讨大黄素对肝内胆汁淤积大鼠的保护作用. 中华中医药学刊, 2026 , 44 (7) : 246 -251 . DOI: 10.13193/j.issn.1673-7717.2026.07.045

Yijing LIU, Hengpan YAO, Suli LI, Fang ZHOU. Discussion on Protective Effect of Emodin on Intrahepatic Cholestasis in Rats Based on TIPE2/TLR4-NF-κB Pathway[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (7) : 246 -251 . DOI: 10.13193/j.issn.1673-7717.2026.07.045

基金

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河南省医学科技攻关省部共建重点计划项目(SBGJ202002125)
河南省科技攻关计划项目(232102311124)

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2026年第44卷第7期

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doi: 10.13193/j.issn.1673-7717.2026.07.045

首发时间：2026-10-20
出版时间：2026-07-10

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河南省医学科技攻关省部共建重点计划项目(SBGJ202002125)

河南省科技攻关计划项目(232102311124)

作者信息

郑州大学附属儿童医院，河南省儿童医院郑州儿童医院，河南　郑州　450053

通讯作者:

周方（1978-），女，河南郑州人，主任医师，硕士研究生导师，硕士，研究方向：儿童消化系统疾病的中西医诊疗。E-mail：zf78@163.com。

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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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