苓桂术甘汤与茵陈蒿汤合方对非酒精性脂肪性肝炎大鼠Nrf2/ARE信号通路的影响

郭一; 李军祥; 毛堂友; 陈晨; 谢添弘; 韩亚飞; 石磊; 谭祥; 韩海啸

doi:10.13422/j.cnki.syfjx.2017160108

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苓桂术甘汤与茵陈蒿汤合方对非酒精性脂肪性肝炎大鼠Nrf2/ARE信号通路的影响

药理 | 更新时间：2024-01-04

- 苓桂术甘汤与茵陈蒿汤合方对非酒精性脂肪性肝炎大鼠Nrf2/ARE信号通路的影响
- Effect of Combined Prescription of Linggui Zhugan Tang and Yinchenhao Tang on Nrf2/ARE Signaling Pathway in Rats with Non-alcoholic Steatohepatitis
- 中国实验方剂学杂志 2017年23卷第16期页码：108-113
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金青年基金项目（81503549）;北京中医药大学自主选题中青年教师项目（2015-JYB-JSMS-110）;北京中医药大学自主选题在读研究生项目（2016-JYB-XS170）
- DOI：10.13422/j.cnki.syfjx.2017160108
  中图分类号： R285.5
- 纸质出版日期：2017
- 稿件说明：
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郭一, 李军祥, 毛堂友, 等. 苓桂术甘汤与茵陈蒿汤合方对非酒精性脂肪性肝炎大鼠Nrf2/ARE信号通路的影响[J]. 中国实验方剂学杂志, 2017,23(16):108-113.

GUO Yi, LI Jun-xiang, MAO Tang-you, et al. Effect of Combined Prescription of Linggui Zhugan Tang and Yinchenhao Tang on Nrf2/ARE Signaling Pathway in Rats with Non-alcoholic Steatohepatitis[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(16): 108-113.
郭一, 李军祥, 毛堂友, 等. 苓桂术甘汤与茵陈蒿汤合方对非酒精性脂肪性肝炎大鼠Nrf2/ARE信号通路的影响[J]. 中国实验方剂学杂志, 2017,23(16):108-113. DOI： 10.13422/j.cnki.syfjx.2017160108.

GUO Yi, LI Jun-xiang, MAO Tang-you, et al. Effect of Combined Prescription of Linggui Zhugan Tang and Yinchenhao Tang on Nrf2/ARE Signaling Pathway in Rats with Non-alcoholic Steatohepatitis[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(16): 108-113. DOI： 10.13422/j.cnki.syfjx.2017160108.

摘要

目的：从氧化应激的角度，观察苓桂术甘汤与茵陈蒿汤合方对非酒精性脂肪性肝炎（NASH）大鼠的干预效应，并通过Nrf2/ARE信号通路探讨合方对非酒精性脂肪性肝炎（NASH）大鼠的作用机制。方法：将SPF级SD大鼠随机分为正常组，模型组，合方组（6.93 g·kg-1），苓桂术甘汤组（3.465 g·kg-1），茵陈蒿汤组（3.465 g·kg-1），莱菔硫烷组（0.5 mg·kg-1），采用高脂饲料法建立NASH模型；高脂饲料饲养8周并同时给药，取材检测大鼠血清丙氨酸氨基转移酶（ALT），天门冬氨酸氨基转移酶（AST）以及血脂总胆固醇（total cholesterol，TC），甘油三酯（triglyceride，TG），高密度脂蛋白胆固醇（high-density lipoprotein，HDL-C），低密度脂蛋白胆固醇（low density lipoprotein，LDL-C）水平，取部分肝组织进行苏木素-伊红（HE）染色，蛋白质免疫印迹（Western blot）与逆转录PCR（RT-PCR）法测定肝脏细胞质接头蛋白1（Kelch-like ECH-associated protein 1，Keap1），核因子E2-关联因子2（nuclear factor E2-related factor 2，Nrf2），醌氧化还原酶1（quinone oxidoreductase-1，NQO1），血红素加氧酶1（heme oxygenase-1，HO-1）蛋白与mRNA表达水平。结果：给药后，与正常组比较，模型组大鼠血脂TC，TG，HDL-C，LDL-C及血清ALT，AST水平升高，肝脏脂肪变明显，肝脏Keap1表达量降低，Nrf2，NQO1，HO-1蛋白与mRNA表达量升高（P <0.05）；与模型组比较，各给药组血脂TC，TG，HDL-C，LDL-C及血清ALT，AST水平有不同程度降低，肝脏病理学也有不同程度改善，除茵陈蒿汤组变化不明显外，各给药组大鼠肝脏Nrf2，NQO1，HO-1蛋白与mRNA表达量均有不同程度升高（P <0.05，P <0.01）；但对于Keap1的表达无明显作用。结论：苓桂术甘汤以及合方可能通过激活Nrf2/ARE信号通路，从而达到改善氧化应激，防治非酒精性脂肪性肝炎的目的。

Abstract

Objective: To observe the effects of combined prescription of Linggui Zhugan Tang (LGZGT) and Yinchenhao Tang (YCHT) on Nrf2/ARE signaling pathway in rats with non-alcoholic steatohepatitis (NASH) from the perspective of oxidative stress

and investigate its mechanism for treating non-alcoholic steatohepatitis. Method: SPF grade SD rats were randomly divided into normal control group

model group

sulforaphane group (0.5 mg·kg-1)

LGZGT group (3.465 g·kg-1)

YCHT group (3.465 g·kg-1) and LGZGT+YCHT combination group (6.93 g·kg-1). High-fat diet was given to establish NASH models

and the treatment was given at the same time for 8 weeks. Then the serum was harvested separately to detect the levels of alanine aminotransferase (ALT)

aspartate aminotransferase (AST)

total cholesterol (TC)

triglyceride (TG)

high-density lipoprotein (HDL-C)

and low density lipoprotein (LDL-C); part liver tissues were taken for HE staining; Western blot and reverse transcription PCR were used respectively to detect the protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (Keap1)

nuclear factor E2-related factor 2 (Nrf2)

quinone oxidoreductase-1 (NQO1)

and heme oxygenase-1 (HO-1). Result: As compared with normal control group

the levels of TC

HDL-C and LDL-C in blood lipid and ALT

AST levels in serum were increased;liver fat became obvious; the expression level of Keap1 in liver was decreased; and

Nrf2

NQO1

HO-1 protein and mRNA expression levels were increased in the model group (P <0.05).As compared with the model group

the levels of TC

HDL-C and LDL-C in blood lipid and ALT

AST levels in serum were decreased in various treatment groups

liver pathology was also improved to some extent; and Nrf2

NQO1

HO-1 protein and mRNA expression levels were increased in treatment groups (P <0.01

P <0.05) except YCHT group. However

the levels of Keap1 didn't show obvious differences among the treatment groups. Conclusion: LGZGT and its combination formula may improve oxidative stress to prevent and treat NASH via activating Nrf2/ARE signaling pathway in the liver.

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