Effect of Chaijie Yiganxian on Hepatic Fibrosis Induced by Thioacetamide in Rats

Hui-jun GUO; Yue-qing CAI; Wei WEI; Xiao-ling YU; Zhi-bi ZHANG; Li-yun JIANG

doi:10.13422/j.cnki.syfjx.20190404

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Effect of Chaijie Yiganxian on Hepatic Fibrosis Induced by Thioacetamide in Rats

Pharmacology | 更新时间：2021-02-09

- Effect of Chaijie Yiganxian on Hepatic Fibrosis Induced by Thioacetamide in Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 4, Pages: 109-115(2019)
- 作者机构：
  
  1.云南中医学院，昆明　 650500；
  2.昆明市中医医院，昆明　 650000；
  3.昆明医科大学　生物医学工程研究中心，昆明　 650500
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190404
  CLC： R2-0;R22;R285.5;R289
- Received：30 July 2018，
  
  Published Online：06 November 2018，
  
  Published：20 February 2019
- 稿件说明：
移动端阅览
Hui-jun GUO, Yue-qing CAI, Wei WEI, et al. Effect of Chaijie Yiganxian on Hepatic Fibrosis Induced by Thioacetamide in Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(4): 109-115.
DOI：

Hui-jun GUO, Yue-qing CAI, Wei WEI, et al. Effect of Chaijie Yiganxian on Hepatic Fibrosis Induced by Thioacetamide in Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(4): 109-115. DOI： 10.13422/j.cnki.syfjx.20190404.

摘要

目的：

研究中药复方柴竭抑肝纤(Chaijie Yiganxian

CJYGX)对抗大鼠肝纤维化的作用及其机制。

方法：

60只SD大鼠随机分为正常组，模型组，阳性组(鳖甲煎丸)，CJYGX高、中、低剂量组。除正常组外，其余5组通过腹腔注射硫代乙酰胺(thioacetamide

TAA)诱导建立肝纤维化模型。自造模第4周开始，阳性组给予鳖甲煎丸1 g·kg

－1

·d

－1

灌胃，CJYGX高、中、低剂量组分别给予CJYGX 7.96，3.98，1.99 g·kg

－1

·d

－1

灌胃，模型组灌服生理盐水，每日灌胃1次，共5周。于末次灌胃24 h后，水合氯醛轻度麻醉大鼠，留取血清及肝组织，称肝脏湿重并计算肝脏指数；全自动分析法检测大鼠肝功能指标丙氨酸氨基转移酶(alanine transaminase

ALT)，天门冬氨酸氨基转移酶(aspartate aminotransferase

AST)，碱性磷酸酶(alkaline phosphatase

ALP)；酶联免疫吸附测定(ELISA)检测肝纤维化血清学标志物层粘连蛋白(laminin

LN)，透明质酸酶(hyaluronidase

HA)，Ⅳ型胶原(Ⅳ collagen

CⅣ)，Ⅲ型前胶原(procollagen Ⅲ， PCⅢ)；马松(Masson)染色观察肝脏纤维化程度；实时荧光定量聚合酶链式反应(Real-time PCR)检测肝脏组织转化生长因子-

(transforming growth factor-

，TGF-

)，Smad2，Smad3，Smad4，Smad7 mRNA表达；免疫组化检测肝脏组织血小板源性生长因子(platelet derived growth factor，PDGF)和TGF-

蛋白表达水平；蛋白免疫印迹法(Western blot)检测肝脏TGF-

和

-平滑肌肌动蛋白(

-SMA)蛋白表达。

结果：

与正常组比较，模型组肝脏指数显著升高；肝功能指标ALP，AST，ALT的含量显著升高；肝纤维化指标LN，HA，Ⅳ-C，PCⅢ和HYP显著升高；Masson染色观察到肝纤维化程度显著增加；TGF-

，Smad2，Smad3，Smad4 mRNA表达显著升高，Smad7 mRNA表达显著降低；TGF-

，PDGF和

-SMA蛋白表达显著升高(

0.01)。与模型组比较，各剂量的CJYGX能不同程度的降低肝功能指标ALP，AST，ALT的水平；肝纤维化指标LN，HA，Ⅳ-C，PCⅢ和HYP都明显的降低；Masson组织观察到肝纤维化程度显著减轻；TGF-

，Smad2，Smad3，Smad4 mRNA表达明显下调，Smad7 mRNA表达明显上调；TGF-

，PDGF和

-SMA蛋白表达显著下调(

0.05，

0.01)。

结论：

中药复方“柴竭抑肝纤”可能通过干预TGF-

/Smad信号通路，保护TAA诱导的大鼠肝纤维化损伤。

Abstract

Objective:

To research the effect of traditional Chinese medicine compound Chaijie Yiganxian (CJYGX) on the hepatic fibrosis in rats and explore the mechanism.

Method:

Totally 60 SD rats were randomly divided into normal group

model group

positive group (Biejia Jianwan)

and low

medium and high-dose CJYGX groups. Except for the normal group

the remaining five groups were involved in establishing the hepatic fibrosis model through the intraperitoneal injection of thioacetamide (TAA). Fourth weeks after modeling

the positive group was given Biejiajian pill (1 g·kg

-1

·d

-1

)

and high

medium and low-dose CJYGX groups were given CJYGX(7.96

3.98

1.99 g·kg

-1

·d

-1

)

respectively. The model group was given normal saline once a day for 5 weeks. 24 h after the last intragastric administration with chloral hydrate

the rats were anesthetized slightly. Serum and liver tissues were collected. The liver wet weight was weighed electronically

and the liver index was calculated. Liver function indexes [alanine transaminase (ALT)

aspartate aminotransferase (AST)

alkaline phosphatase (ALP)] and serum markers [laminin (LN)

hyaluronidase (HA)

Ⅳ collagen (CⅣ)

procollagen Ⅲ (PCⅢ)]

of hepatic fibrosis were detected by enzyme linked immunosorbent assay (ELISA). The degree of hepatic fibrosis by Masson stain

mRNA expressions of transforming growth factor-

(TGF-

)

Smad2

Smad3

Smad4

Smad7 were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR)

and protein expression levels of platelet derived growth factor (PDGF)

TGF-

and

-smooth muscle actin (

-SMA) were detected by immunohistochemical or Western blot.

Result:

Compared with the blank group

the model group liver index was significantly increased; the contents of ALP

AST and ALT were significantly increased; the liver fibrosis indexes LN

Ⅳ-C

PCⅢ and HYP were significantly increased; the degree of liver fibrosis was significantly increased in Masson tissue; the mRNA expressions of TGF-

Smad2

Smad3

Smad4 were significantly increased; and the Smad7 mRNA expression was significantly decreased. The protein expressions of TGF-

PDGF and

-SMA increased significantly (

0.01). Compared with model group

different doses of CJYGX can reduce the concentrations of ALP

AST

ALT

and the hepatic fibrosis indexes (LN and HA

Ⅳ-C

PCⅢ) and HYP also were significantly lower. Masson staining show that CJYGX can significantly reduce the degree of hepatic fibrosis. Real-time PCR show that CJYGX can significantly down-regulate mRNA expressions of TGF-

Smad2

Smad3

Smad4 and up-regulate mRNA expression of Smad7.Immunohistochemical and Western blot analysis show that

compared with model group

CJYGX could significantly reduce the protein expressions of TGF-

PDGF and

-SMA (

0.05

0.01).

Conclusion:

Traditional Chinese medicine compound CJYGX may protect TAA-induced hepatic fibrosis injury by interfering with TGF-

/Smad signaling pathway.

关键词

Keywords

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