Effect of Jiedu Hugan Decoction on Protein Expression of MIP-2 and MIP-1β in Rats with Drug-induced Liver Injury

Chen-xu LIU; Xi WANG; Yi-xin ZHANG; Xin-qiao CHU; Wei-wei HU; Qiu-hong GUO; Xue HAN; Ya-ning BIAO

doi:10.13422/j.cnki.syfjx.20191938

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Effect of Jiedu Hugan Decoction on Protein Expression of MIP-2 and MIP-1β in Rats with Drug-induced Liver Injury

Pharmacology | 更新时间：2021-02-09

- Effect of Jiedu Hugan Decoction on Protein Expression of MIP-2 and MIP-1β in Rats with Drug-induced Liver Injury
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 18, Pages: 57-64(2019)
- 作者机构：
  
  1.河北中医学院　药学院，河北省高校中药组方制剂应用技术研究中心，石家庄　 050200；
  2.石家庄医学高等专科学校，石家庄　 050599
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191938
  CLC： R2-0; R285.5; R289
- Published：20 September 2019，
  
  Published Online：25 June 2019，
  
  Received：16 April 2019，
- 稿件说明：
扫描看全文
Chen-xu LIU, Xi WANG, Yi-xin ZHANG, et al. Effect of Jiedu Hugan Decoction on Protein Expression of MIP-2 and MIP-1β in Rats with Drug-induced Liver Injury. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(18):57-64(2019)
DOI：

Chen-xu LIU, Xi WANG, Yi-xin ZHANG, et al. Effect of Jiedu Hugan Decoction on Protein Expression of MIP-2 and MIP-1β in Rats with Drug-induced Liver Injury. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(18):57-64(2019) DOI： 10.13422/j.cnki.syfjx.20191938.

摘要

目的：

通过检测大鼠血清肝功能、血清生物标志物，炎性因子以及巨噬细胞炎性蛋白-2(MIP-2)，巨噬细胞炎性蛋白-1

(MIP-1

)的表达，观察解毒护肝汤对药物性肝损伤大鼠的干预作用及机制。

方法：

采用灌服对乙酰氨基酚方法复制药物性肝损伤大鼠模型，将Wistar大鼠按体质量随机分为正常组，模型组，水飞蓟宾组(44.1 mg·kg

－1

)，解毒护肝汤高、中、低剂量组(63，31.5，15.75 g·kg

－1

)，正常组和模型组给予生理盐水灌胃，其余各组给予相应药液灌胃，连续给药30 d。实验结束后，腹主动脉取血分离血清检测天门冬氨酸氨基转移酶(AST)，丙氨酸氨基转移酶(ALT)，总胆红素(TBIL)，直接胆红素(DBIL)，苹果酸脱氢酶(MDH)，对氧磷酶1(PON1)，谷氨酸脱氢酶(GLDH)，精氨酸(ARG)，嘌呤核苷酸磷酸化酶(PNP)，肿瘤坏死因子-

(TNF-

)，白细胞介素-6(IL-6)的含量；苏木素-伊红(HE)染色法观察肝组织病理形态改变；免疫组化法观察MIP-1

的蛋白表达情况；用单荧光免疫组化观察MIP-2的蛋白表达情况；用酶联免疫吸附测定(ELISA)检测肝组织匀浆中TNF-

和IL-6的含量。

结果：

与正常组比较，模型组大鼠血清AST，ALT，DBIL，PON1，ARG，GLDH，MDH，PNP，TNF-

含量均明显升高(

0.05，

0.01)，肝组织MIP-2，MIP-1

蛋白阳性表达增多；与模型组比较，解毒护肝汤中、低剂量组能明显降低转氨酶活性及胆红素含量(

0.05，

0.01)，解毒护肝汤高剂量组能明显降低肝损伤大鼠血清PON1，MDH和TNF-

的含量(

0.05)，解毒护肝汤中剂量组明显降低ARG，MDH的含量(

0.05)，解毒护肝汤高、中剂量组均能明显降低肝组织MIP-2，MIP-1

蛋白的表达，解毒护肝汤中剂量组效果最优，各给药组对肝细胞病理形态均具有不同程度的保护作用。

结论：

解毒护肝汤中剂量组的护肝效果较优，且其作用机制可能通过降低TNF-

的含量，进而影响趋化因子MIP-2和MIP-1

对中性粒细胞的趋化，抑制炎性因子的释放，从而预防炎症发生。

Abstract

Objective:

To observe the effect and mechanism of Jiedu Hugan decoction on drug-induced liver injury in rats by detecting serum liver function

serum biomarkers

inflammatory factors

macrophage inflammatory protein-2 (MIP-2) and macrophage inflammatory protein-1

(MIP-1

Method:

The rat model of drug-induced liver injury was induced by acetaminophen (1 g·kg

-1

) orally once daily for 30 days. The sixty male adult Wistar rats were divided into five groups

control group

model group

administered silybin group(44.1 mg·kg

-1

)

Jiedu Hugan decoction high

medium and low dose groups (63

31.5

15.75 g·kg

-1

)

normal group and model group were given normal saline gavage

and the other groups were given corresponding liquid gavage for 30 days. After the experiment

the abdominal aorta separation take blood serum aspartate amino transferase (AST)

alanine aminotransferase (ALT)

total bilirubin (TBIL)

direct bilirubin (DBIL)

malate dehydrogenase (MDH)

enzyme for oxygen p1 (PON1) and glutamate dehydrogenase (GLDH)

arginine (ARG)

purine nucleotide phosphorylase (PNP)

tumor necrosis factor-

(TNF-

)

interleukin-6(IL-6) content. Pathological morphological changes of liver tissues were observed by hematoxylin-eosin (HE) staining. The protein expression of MIP-1

was observed by immunohistochemistry. The protein expression of MIP-2 was observed by single fluorescence immunohistochemistry

and the contents of TNF-

and IL-6 in liver homogenate were detected by enzyme-linked immunosorbent assay (ELISA).

Result:

Compared with normal group

levels of AST

ALT

DBIL

PON1

ARG

GLDH

MDH

PNP and TNF-

in model group were significantly increased (

0.05

0.01). Compared with model group

detoxification

Jiedu Hugan decoction low dose group can obviously decrease transaminase activity and content of bilirubin (

0.05

0.01). Jiedu Hugan decoction high dose group can significantly reduce the levels of PON1

MDH and the content of TNF-

in liver injury rats(

0.05)

Jiedu Hugan decoction low dose group significantly reduce the levels of ARG

MDH (

0.05)

Jiedu Hugan decoction high

middle dose group can obviously reduce the liver tissue MIP-2

MIP-1

protein expression

detoxification protect liver soup effect of the optimal dose group

the pathological morphology of liver cell dosage group were with different degree of protection.

Conclusion:

The effect of Jiedu Hugan decoction in medium dose group is better

and its mechanism may affect the chemotaxis of neutrophils induced by MIP-2 and MIP-1

by reducing the content of TNF-

thus inhibiting the release of inflammatory factors and preventing inflammation.

关键词

药物性肝损伤解毒护肝汤巨噬细胞炎性蛋白-2巨噬细胞炎性蛋白-1β

Keywords

drug-induced liver injuryJiedu Hugan decoctionmacrophage inflammatory protein(MIP)-2MIP-1β

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