加味四逆散对抑郁模型大鼠肝损伤的保护作用

陈新; 牟雄军; 刘昊; 刘焱文; 刘松林

doi:10.13422/j.cnki.syfjx.20201822

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加味四逆散对抑郁模型大鼠肝损伤的保护作用

经典名方 | 更新时间：2020-09-09

- 加味四逆散对抑郁模型大鼠肝损伤的保护作用
- Protective Effect of Modified Sinisan on Depression-induced Liver Injury in Rat
- 中国实验方剂学杂志 2020年26卷第18期页码：18-23
- 作者机构：
  
  湖北中医药大学，中药资源与中药化学湖北省重点实验室，武汉 430065
- 作者简介：
  
  陈新，副研究员，从事中药药效物质基础研究，E-mail：chenxin30172@hotmail.com
  刘松林，教授，从事经方防治消化及心血管疾病的临床基础研究，E-mail：newforest@163.com
- 基金信息：
  
  湖北省教育厅科学技术研究项目(Q20182009)
- DOI：10.13422/j.cnki.syfjx.20201822
  中图分类号： R22;R242;R284.1;R285.5
- 收稿日期：2020-01-23，
  
  网络出版日期：2020-07-16，
  
  纸质出版日期：2020-09-20
- 稿件说明：
移动端阅览
陈新,牟雄军,刘昊等.加味四逆散对抑郁模型大鼠肝损伤的保护作用[J].中国实验方剂学杂志,2020,26(18):18-23.

CHEN Xin,MOU Xiong-jun,LIU Hao,et al.Protective Effect of Modified Sinisan on Depression-induced Liver Injury in Rat[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(18):18-23.
陈新,牟雄军,刘昊等.加味四逆散对抑郁模型大鼠肝损伤的保护作用[J].中国实验方剂学杂志,2020,26(18):18-23. DOI： 10.13422/j.cnki.syfjx.20201822.

CHEN Xin,MOU Xiong-jun,LIU Hao,et al.Protective Effect of Modified Sinisan on Depression-induced Liver Injury in Rat[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(18):18-23. DOI： 10.13422/j.cnki.syfjx.20201822.

摘要

目的

研究加味四逆散对慢性温和不可预知性应激（CUMS）结合孤养法制作抑郁模型所致肝损伤的保护作用。

方法

将48只SD雄性大鼠随机分为6组，正常组，抑郁模型组，氟西汀（1.58 mg·kg

-1

·d

-1

）组，和加味四逆散低、中、高剂量（3.67，7.34，14.68 g·kg

-1

·d

-1

）组，每组8只。造模给药结束后，采用生化试剂盒法检测各组大鼠血清中丙氨酸氨基转移酶（ALT），天冬氨酸氨基转移酶（AST）水平和肝脏组织中炎症因子肿瘤坏死因子-

（TNF-

），白细胞介素-1

（IL-1

），白细胞介素-6（IL-6）水平。采用蛋白免疫印迹法（Western blot）检测加味四逆散对肝细胞中半胱氨酸蛋白酶-3（Caspase-3），活化型半胱氨酸蛋白酶-3（cleaved Caspase-3）蛋白表达的干预作用。

结果

生化试剂盒检测显示，与正常组比较，模型组大鼠血清中的ALT，AST水平明显升高（

0.05），肝脏组织中炎症因子TNF-

，IL-1

和IL-6水平明显升高（

0.05）；与模型组比较，加味四逆散低、中剂量组可降低血清中ALT，AST和炎症因子TNF-

，IL-1

和IL-6水平（

0.05，

0.01）。Western blot检测显示，与正常组比较，模型大鼠肝细胞中的Caspase-3蛋白表达下降，cleaved Caspase-3蛋白表达上升（

0.05）；与模型组比较，加味四逆散低、中剂量组可以上调Caspase-3蛋白的表达，下调cleaved Caspase-3蛋白的表达（

0.05，

0.01）。

结论

慢性应激反应所致抑郁模型可造成肝损伤，加味四逆散能够通过调节多种生理生化和炎症因子指标的水平，抑制肝脏细胞凋亡来达到保肝作用。

Abstract

Objective

To study the protective effect of modified Sinisan on liver injury caused by chronic unpredictable mild stress (CUMS) combined with solitary nutrition method based on a depression model.

Method

Forty-eight SD male rats were randomly divided into normal group

depression model group

fluoxetine group (1.58 mg·kg

-1

·d

-1

)

and low

medium and high-dose modified Sinisan (3.67

7.34

14.68 g·kg

-1

·d

-1

) groups

with 8 rats in each group. After the administration of the model

the levels of alanine aminotransferase（ALT）

aspartate aminotransferase（AST） in serum and the levels of inflammatory factors tumor necrosis factor-

（TNF-

）

interleukin（IL）-1

and IL-6 in liver tissues were measured by a biochemical kit method. Western blot was used to detect the expressions of cysteine aspastic acid-specific protease-3 (Caspase-3) and cleaved Caspase-3 in liver cells after intervention with modified Sinisan.

Result

Compared with the normal group

the biochemical test showed that the levels of ALT and AST in the serum of the model group were significantly increased (

0.05)

and the levels of inflammatory factors TNF-

IL-1

and IL-6 in liver tissue significantly increased (

0.05). Compared with the model group

low

medium-dose modified Sinisan groups significantly reduced serum ALT

AST and inflammatory factors TNF-

IL-1

and IL-6 levels (

0.05). Western blot showed that compared with the normal group

the protein expression of Caspase-3 in model rat liver cells decreased

while the protein expression of cleaved Caspase-3 increased（

0.05，

0.01）. Compared with the model group

low

medium-dose modified Sinisan groups could up-regulate Caspase-3 protein expression

and down-regulated the expression of cleaved Caspase-3 protein（

0.05，

0.01）.

Conclusion

Chronic stress-induced depression model can cause liver damage. Modified Sinisan can have the hepatoprotective effect by regulating the levels of various physiological

biochemical and inflammatory factor indicators

and inhibiting liver cell apoptosis.

关键词

Keywords

references

ZHOU M , WANG H , ZENG X , et al . Mortality, morbidity, and risk factors in China and its provinces, 1990—2017: a systematic analysis for the Global Burden of Disease Study 2017 [J]. Lancet , 2019 , 394 ( 10204 ): 1145 - 1158 .

FRANKISH H , BOYCE N , HORTON R . Mental health for all: a global goal [J]. Lancet , 2018 , 392 ( 10157 ): 1493 - 1494 .

王世锴 , 李良 , 郭萍 , 等 . 抑郁症家族史及心理应激对首发抑郁症急性期疗效的影响 [J]. 中国慢性病预防与控制 , 2017 , 25 ( 9 ): 702 - 705 .

JAWAD A Z , OLE G , MICHAEL T M , et al . Prevention of depression in patients with cancer: a systematic review and Meta-analysis of randomized controlled trials [J]. J Psychiatr Res , 2020 , 120 ( 1 ): 113 - 123 .

GRIFFIN A T , FLORIN V , SIDNEY Z , et al . Clinical correlates of depression chronicity among people living with HIV: what is the role of suicidal ideation? [J]. J Affective Disord , 2019 , 258 ( 1 ): 163 - 171 .

KAI G K , BRITTA S , HELGE F . Link between depression and cardiovascular diseases due to epigenomics and proteomics: focus on energy metabolism [J]. Prog Neuropsychopharmacol Biol Psychiatry , 2019 , 89 ( 1 ): 146 - 157 .

QIN X , WU Z , DONG J , et al . Liver soluble epoxide hydrolase regulates behavioral and cellular effects of chronic stress [J]. Cell Rep , 2019 , 29 ( 10 ): 3223 - 3234，3236 .

JENNIFER R R , MARIYA T , GEORGIA E H . Deciphering sex diﬀerences in the immune system and depression [J]. Front Neuroendocrinol , 2018 , 50 ( 1 ): 67 - 90 .

牟雄军 , 刘昊 , 林宁 , 等 . 疏肝和胃汤及其有效物质部位对抑郁模型大鼠下丘脑内多种神经递质含量的影响 [J]. 中国中药杂志 , 2019 , 44 ( 15 ): 3343 - 3348 .

牟雄军 , 明浩 , 许乐思 , 等 . 疏肝和胃汤抗抑郁作用有效物质部位筛选及其对海马内多种神经递质含量影响的研究 [J]. 中国中药杂志 , 2019 , 44 ( 3 ): 526 - 534 .

WILLNER P , TOWELL A , SAMPSON D , et al . Reduction of sucrose preference by chronic unpredictable mild stress and its restoration by a tricyclic antidepressant [J]. Psychopharmacology , 1987 , 93 ( 3 ): 358 - 364 .

魏伟 , 吴希美 , 李元建 . 药理实验方法学 [M]. 4版 . 北京 : 人民卫生出版社 , 2010 : 1439 - 1442 .

李君玲 . 基于慢性不可预知温和应激大鼠模型的“肝主疏泄”生物学基础研究 [D]. 北京：北京中医药大学 , 2016 .

SHIELDS G S . Stress and cognition: a user's guide to designing and interpreting studies [J]. Psychoneuroendocrinology , 2020 , 112 ( 104475 ): 1 - 13 .

TSUKAMOTO K , MACHIDA K . Effects of psychological stress on neutrophil phagocytosis and bactericidal activity in humans-a Meta-analysis [J]. Int J Psychophysiol , 2014 , 91 ( 2 ): 67 - 72 .

LUCIA G , STEFANO G , RANKA V , et al . Impact of psychosocial status on liver transplant process [J]. Ann Hepatol , 2019 , 18 ( 6 ): 804 - 809 .

刘晨 , 汤冬静 . 血脂血清学指标与肝功能检验应用于脂肪肝诊断中的效果分析 [J]. 中国医药指南 , 2019 , 17 ( 19 ): 111 - 112 .

MAHMOUD M , PAUL M , ANDRES F C . Hepatic complications of inflammatory bowel disease [J]. Clin Liver Dis , 2019 , 23 ( 2 ): 191 - 208 .

SIMPSON W ， STEINER M ， COOTE M ， et al . Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study [J]. Rev Bras Psiquiatr , 2016 , 38 ( 3 ): 190 - 196 .

SHELTON M M ， SCHMINKEY D L ， GROER M W . Relationships among prenatal depression，plasma cortisol，and inflammatory cytokines [J]. Biol Res Nurs , 2015 , 17 ( 3 ): 295 - 302 .

LIU J , WANG F , YIN D , et al . Caspase 3 may participate in the anti-tumor immunity of dendritic cells [J]. Biochem Biophys Res Commun , 2019 , 511 ( 2 ): 447 - 453 .

OPDENBOSCH N V , LAMKANFI M . Caspases in cell death, inflammation, and disease [J]. Immunity , 2019 , 50 ( 6 ): 1352 - 1364 .

柳小远 , 盛梅笑 . 治疗慢性肾脏病常用中草药相关肝损伤研究进展 [J]. 中华中医药杂志 , 2019 , 34 ( 9 ): 4210 - 4213 .

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