Mechanism of Zhizi Prescription in Protection of CCl<sub>4</sub>-induced Acute and Subacute Liver Injury in Mice

Yanlei ZHANG; Longtao CUI; Qiyao WANG; Liping CHEN; Yong ZHANG; Jiatuo XU; Weiliang ZHU; Zhangbin GONG; Kaixian CHEN

doi:10.13422/j.cnki.syfjx.20221206

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Mechanism of Zhizi Prescription in Protection of CCl₄-induced Acute and Subacute Liver Injury in Mice

更新时间：2022-08-11

- Mechanism of Zhizi Prescription in Protection of CCl₄-induced Acute and Subacute Liver Injury in Mice
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 18, Pages: 30-37(2022)
- 作者机构：
  
  1.上海中医药大学基础医学院，上海 201203
  2.上海中医药大学中药学院，上海 201203
  3.中国科学院上海药物研究所，上海 201203
  4.中国科学院大学，北京 100049
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20221206
  CLC： R2-0;R22;R285.5;R289;R33
- Published：20 September 2022，
  
  Published Online：16 May 2022，
  
  Received：05 January 2022，
- 稿件说明：
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张艳蕾,崔龙涛,王琪瑶等.食源性栀子方保护CCl₄诱导小鼠急性和亚急性肝损伤的机制[J].中国实验方剂学杂志,2022,28(18):30-37.

ZHANG Yanlei,CUI Longtao,WANG Qiyao,et al.Mechanism of Zhizi Prescription in Protection of CCl₄-induced Acute and Subacute Liver Injury in Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):30-37.
张艳蕾,崔龙涛,王琪瑶等.食源性栀子方保护CCl₄诱导小鼠急性和亚急性肝损伤的机制[J].中国实验方剂学杂志,2022,28(18):30-37. DOI： 10.13422/j.cnki.syfjx.20221206.

ZHANG Yanlei,CUI Longtao,WANG Qiyao,et al.Mechanism of Zhizi Prescription in Protection of CCl₄-induced Acute and Subacute Liver Injury in Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):30-37. DOI： 10.13422/j.cnki.syfjx.20221206.

摘要

目的

探讨食源性栀子方（ZZP）对四氯化碳（CCl

）所致急性和亚急性肝损伤的保护作用及机制。

方法

建立急性和亚急性肝损伤动物模型。C57小鼠随机分为正常组、模型组、奥贝胆酸组、食源性栀子方（简称复方）高、低剂量组（0.5、0.25 g·kg

-1

），根据急性、亚急性实验设计，末次给药后，分别收集各组小鼠的血清和肝脏组织。苏木素-伊红（HE）和天狼猩红染色观察肝脏病理变化；试剂盒测定血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBIL），肝匀浆羟脯氨酸（Hyp）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平；酶联免疫吸附测定法（ELISA）检测肝脏组织肿瘤坏死因子-

（TNF-

）和白细胞介素-6（IL-6）的水平；实时荧光定量聚合酶链式反应（Real-time PCR）检测肝组织胶原1a1（Col1a1）、胶原3a1（Col3a1）、纤维连接蛋白（FN）、转化生长因子

受体Ⅱ（Tgfbr2）及

-平滑肌肌动蛋白（

-SMA） mRNA表达。

结果

急性肝损伤：与正常组比较，模型组小鼠的ALT、AST、TBIL、MDA、水平均显著升高（

0.01），肝SOD酶活性显著性降低（

0.01）。与模型组比较，复方高、低剂量组复方可明显降低肝细胞损伤程度，均能保护CCl

所诱导的急性肝损伤，复方高剂量组效果优于低剂量组。亚急性肝损伤：模型组小鼠的ALT、AST、MDA、TNF-

和IL-6水平均显著升高（

0.01），肝SOD酶活性显著降低（

0.01）。与模型组小鼠比较，复方高、低剂量组肝脏Hyp含量显著降低（

0.01），两组肝组织胶原沉积程度明显减轻，复方高剂量组亦可明显下调小鼠肝脏

-SMA、Col1a1、Col3a1、FN和Tgfbr2 mRNA表达（

0.05，

0.01）。

结论

复方可有效保护CCl

诱导的急性和亚急性肝损伤，保护效应与浓度成正比，其机制可能与增加肝组织抗氧化酶的活性，降低脂质过氧化水平，抑制炎性反应有关，从而减少胶原沉积，改善早期肝纤维化。

Abstract

Objective

To investigate the protective effect of Zhizi prescription （ZZP） on carbon tetrachloride （CCl

）-induced acute and subacute liver injury and its mechanism.

Method

Acute and subacute liver injury animal models were induced. C57 mice were randomly divided into a normal group， model group， obeccholic acid group， ZZP high-dose （0.5 g·kg

-1

） group， and ZZP low-dose （0.25 g·kg

-1

） group. According to the experiment design， the serum and liver tissue of mice were collected after the last administration. Hematoxylin-eosin （HE） and Sirius staining was used to observe the liver pathological changes. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBIL）， liver homogenate hydroxyproline （Hyp）， malondialdehyde （MDA）， and superoxide dismutase （SOD） levels were determined by kit. The levels of tumor necrosis factor-

（TNF-

） and interleukin-6 （IL-6） in the liver tissue were determined by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expressions of collagen 1A1 （Col1a1）， collagen 3A1 （Col3a1）， fibronectin （FN）， transforming growth factor

receptor Ⅱ （Tgfbr2） and

-smooth muscle actin （

-SMA） in the liver tissue.

Result

In terms of the acute liver injury， as compared with the normal group， the levels of ALT， AST， TBIL and MDA in the model group were significantly increased （

0.01）， while the activity of liver SOD was significantly decreased （

0.01）. Compared with model group， the ZZP high-dose and low-dose groups both significantly reduced the degree of liver cell injury， and protected the acute liver injury induced by CCl

. The ZZP high-dose group had a better effect than the ZZP low-dose group. In terms of the subacute liver injury， the levels of ALT， AST， MDA，TNF-

and IL-6 in the model group were significantly increased （

0.01）， while the activity of liver SOD was significantly decreased （

0.01）. As compared with the model group， liver Hyp content in the ZZP high-dose and low-dose groups was significantly decreased （

0.01）， and the collagen deposition in liver of both groups was significantly reduced. The ZZP high-dose group also significantly down-regulated the mRNA expressions of

-SMA， Col1a1， Col3a1， FN， and Tgfbr2 in the liver of mice （

0.05，

0.01）.

Conclusion

ZZP effectively protects the acute and subacute liver injury induced by CCl

， and the protective effect is proportional to its concentration. The mechanism may be related to the increase of the activity of antioxidant enzymes in the liver tissue， the decrease of the level of lipid peroxidation， and the inhibition of inflammatory response， thus reducing collagen deposition and improving early liver fibrosis.

关键词

药食同源四氯化碳肝损伤抗氧化胶原沉积肝纤维化

Keywords

homology of medicine and foodcarbon tetrachloride （CCl4）liver injuryantioxidantcollagen depositionliver fibrosis

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⁰

Mechanism of Zhizi Prescription in Protection of CCl4-induced Acute and Subacute Liver Injury in Mice

DOI：10.13422/j.cnki.syfjx.20221206

摘要

Abstract

关键词

Keywords

references

Mechanism of Zhizi Prescription in Protection of CCl₄-induced Acute and Subacute Liver Injury in Mice