Babaodan Alleviates APAP-induced Acute Liver Injury in Mice by Inhibiting NLRP3/Caspase-1 Pathway

ZHAO Ruowei; ZHANG Qing; ZHU Mingxing; LIU Yueyang; CHENG Zaixing; HUANG Mingqing; ZHENG Yanfang; LIN Yanxiang

doi:10.13422/j.cnki.syfjx.20222001

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Babaodan Alleviates APAP-induced Acute Liver Injury in Mice by Inhibiting NLRP3/Caspase-1 Pathway

更新时间：2023-02-07

- Babaodan Alleviates APAP-induced Acute Liver Injury in Mice by Inhibiting NLRP3/Caspase-1 Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 5, Pages: 122-128(2023)
- 作者机构：
  
  1.福建中医药大学药学院，福州 350122
  2.福建中医药大学中医学院，福州 350122
  3.福建中医药大学针灸学院，福州 350122
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20222001
  CLC： R2-0;R22;R285.5;R289;R33
- Published：05 March 2023，
  
  Published Online：02 November 2022，
  
  Received：05 August 2022，
- 稿件说明：
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赵若玮,张庆,朱铭星等.八宝丹通过抑制NLRP3/Caspase-1通路减轻对乙酰氨基酚诱导的小鼠急性肝损伤[J].中国实验方剂学杂志,2023,29(05):122-128.

ZHAO Ruowei,ZHANG Qing,ZHU Mingxing,et al.Babaodan Alleviates APAP-induced Acute Liver Injury in Mice by Inhibiting NLRP3/Caspase-1 Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):122-128.
赵若玮,张庆,朱铭星等.八宝丹通过抑制NLRP3/Caspase-1通路减轻对乙酰氨基酚诱导的小鼠急性肝损伤[J].中国实验方剂学杂志,2023,29(05):122-128. DOI： 10.13422/j.cnki.syfjx.20222001.

ZHAO Ruowei,ZHANG Qing,ZHU Mingxing,et al.Babaodan Alleviates APAP-induced Acute Liver Injury in Mice by Inhibiting NLRP3/Caspase-1 Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):122-128. DOI： 10.13422/j.cnki.syfjx.20222001.

摘要

目的

研究八宝丹（BBD）对对乙酰氨基酚（APAP）诱导的急性肝损伤小鼠NOD样受体热蛋白结构域相关蛋白3/胱天蛋白酶-1（NLRP3/Caspase-1）通路蛋白的影响。

方法

将C57BL/6小鼠随机分组，BBD（75、150、300 mg·kg

-1

）灌胃给药3 d，2次/d，于末次给药后2 h，腹腔注射APAP（400 mg·kg

-1

），14 h后摘眼球取血，随后脱颈椎处死取材。苏木素-伊红（HE）染色法观察肝组织细胞形态学变化；生化法检测各组小鼠血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、超氧化物歧化酶（SOD）、丙二醛（MDA）和髓过氧化物酶（MPO）的活性；实时荧光定量聚合酶链式反应（Real-time PCR）检测小鼠肝脏中肿瘤坏死因子-

（TNF-

）、白细胞介素-1

（IL-1

）及白细胞介素-6（IL-6） mRNA表达水平；蛋白免疫印迹法（Western blot）检测小鼠肝脏中环氧化酶-2（COX-2）、诱导型一氧化氮合酶（iNOS）、NLRP3、Caspase-1、白细胞介素-18（IL-18）的蛋白表达水平。

结果

与正常组比较，模型组小鼠肝脏组织小叶结构部分破坏、肝窦扩张，血清中ALT和AST水平，肝组织中NLRP3、Caspase-1、iNOS、IL-18、COX-2蛋白表达水平和IL-1

、IL-6、TNF-

mRNA水平均明显升高（

0.05，

0.01）。与模型组比较，各给药组小鼠肝细胞破裂现象有所好转，肝血窦挤压情况有所缓解，血清中ALT和AST水平，肝组织中NLRP3、Caspase-1、iNOS、IL-18、COX-2蛋白表达水平和IL-1

、IL-6、TNF-

mRNA水平均明显降低（

0.05，

0.01），并呈剂量依赖性。

结论

BBD可减轻APAP诱导的小鼠急性肝损伤，其机制可能与抗氧化应激，抑制NLRP3/Caspase-1通路，进而降低IL-1

、IL-18、TNF-

、IL-6表达水平有关。

Abstract

Objective

To explore the effect of Babaodan （BBD） on the NOD-like receptor pyrin domain containing 3/cysteine aspartate-specific protease-3 （NLRP3/Caspase-1） pathway proteins in mice with acetaminophen （APAP）-induced acute liver injury.

Method

C57BL/6 mice were randomly grouped， and BBD （75， 150， 300 mg·kg

-1

，

） was administered twice a day for three days. After 2 hours of the last administration， the mice were treated with APAP （400 mg·kg

-1

，

）， and the eyeballs were removed to collect blood after 14 hours. Then they were sacrificed by cervical dislocation for sample collection. Hematoxylin-eosin （HE） staining was used to observe the morphological changes of liver tissue cells， and biochemical methods were used to detect the activities of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， superoxide dismutase （SOD）， malondialdehyde （MDA） and myeloperoxidase （MPO） in serum of mice in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to determine the mRNA expression of tumor necrosis factor-

（TNF-

）， interleukin-1

（IL-1

） and IL-6， and Western blot was performed to determine the protein expression of cyclooxygenase-2 （COX-2）， inducible nitric oxide synthase （iNOS）， NLRP3， Caspase-1 and IL-18 in the liver of mice.

Result

Compared with the conditions in normal group， the hepatic lobule structure of mice in the model group was partially destroyed， and the hepatic sinusoids were dilated. And the expression levels of ALT and AST in serum， the protein levels of NLRP3， Caspase-1， iNOS， IL-18 and COX-2 and the mRNA levels of IL-1

， IL-6 and TNF-

were increased （

0.05，

0.01）. Compared with the model group， the administration groups had improvement in liver cell rupture and hepatic sinusoidal compression， and a dose-dependent decrease in the levels of ALT and AST in serum as well as the protein levels of NLRP3， Caspase-1， iNOS， IL-18 and COX-2 and the the mRNA levels of IL-1

， IL-6 and TNF-

in liver tissue （

0.05，

0.01）.

Conclusion

BBD can reduce APAP-induced acute liver injury in mice. The mechanism may be related to anti-oxidative stress， inhibition of NLRP3/Caspase-1 pathway， and decreased expression levels of IL-1

， IL-18， TNF-

and IL-6.

关键词

八宝丹急性肝损伤炎症因子NOD样受体热蛋白结构域相关蛋白3（MRP3）胱天蛋白酶-1（Caspase-1）

Keywords

Babaodanacute liver injuryinflammatory factorsNOD-like receptor pyrin domain containing 3 （NLRP3）cysteine aspartate-specific protease-3 （Caspase-1）

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