Effects of <italic style="font-style: italic">Modified Ditan Decoction</italic> （加味涤痰汤） on Myocardial Tissue Injury and Keap1-Nrf2 Signaling Pathway in Chronic Intermittent Hypoxia Model Rats

Ran LIAO; Qin CHEN; Feng WANG; Dan LIU; Jingyi LI; Fengsheng XU; Yijin WANG; Haiyin ZHENG; Lili CHEN; Runhua WU

doi:10.13288/j.11-2166/r.2022.04.013

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Effects of Modified Ditan Decoction （加味涤痰汤） on Myocardial Tissue Injury and Keap1-Nrf2 Signaling Pathway in Chronic Intermittent Hypoxia Model Rats

更新时间：2022-02-15

- Effects of Modified Ditan Decoction （加味涤痰汤） on Myocardial Tissue Injury and Keap1-Nrf2 Signaling Pathway in Chronic Intermittent Hypoxia Model Rats
- Journal of Traditional Chinese Medicine Vol. 63, Issue 4, Pages: 370-376(2022)
- 作者机构：
  
  福建中医药大学中西医结合学院，福建省福州市闽侯县上街镇邱阳路1号，350122
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2022.04.013
  CLC：
- Received：02 November 2021，
  
  Revised：2021-12-08，
  
  Published：17 February 2022
- 稿件说明：
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廖燃,陈沁,王丰等.加味涤痰汤对慢性间歇低氧模型大鼠心肌组织损伤及Keap1-Nrf2信号通路的影响[J].中医杂志,2022,63(04):370-376.

LIAO Ran,CHEN Qin,WANG Feng,et al.Effects of Modified Ditan Decoction （加味涤痰汤） on Myocardial Tissue Injury and Keap1-Nrf2 Signaling Pathway in Chronic Intermittent Hypoxia Model Rats[J].Journal of Traditional Chinese Medicine,2022,63(04):370-376.
廖燃,陈沁,王丰等.加味涤痰汤对慢性间歇低氧模型大鼠心肌组织损伤及Keap1-Nrf2信号通路的影响[J].中医杂志,2022,63(04):370-376. DOI： 10.13288/j.11-2166/r.2022.04.013.

LIAO Ran,CHEN Qin,WANG Feng,et al.Effects of Modified Ditan Decoction （加味涤痰汤） on Myocardial Tissue Injury and Keap1-Nrf2 Signaling Pathway in Chronic Intermittent Hypoxia Model Rats[J].Journal of Traditional Chinese Medicine,2022,63(04):370-376. DOI： 10.13288/j.11-2166/r.2022.04.013.

摘要

目的

探讨加味涤痰汤对慢性间歇性低氧诱导大鼠心肌损伤的影响及可能作用机制。

方法

30只SD大鼠随机分为正常组、模型组、加味涤痰汤组，每组10只。模型组和加味涤痰汤组放入低氧舱内建立慢性间歇性低氧大鼠模型。加味涤痰汤组每天放进低氧舱前30 min按 14.8 g/（kg·d）灌胃给药，正常组和模型组则按相同体积予生理盐水灌胃，共干预12周。检测血清心肌酶指标［包括肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）］、氧化应激指标［包括丙二醛（MDA）、谷胱甘肽（GSH）］和组织铁含量；检测心肌组织中kelch样ECH关联蛋白1（Keap1）、核红系转录因子2（Nrf2）、谷胱甘肽过氧化物酶4（Gpx4）、酰基辅酶A合成酶长链家族成员4（Acsl4）蛋白和mRNA的表达；HE染色观察心肌细胞的形态。

结果

与正常组比较，模型组大鼠血清CK、CK-MB、LDH、MDA上升，GSH表达和组织铁含量降低，心肌组织Keap1、Acsl4蛋白和mRNA表达增加，Nrf2、Gpx4蛋白和mRNA表达减少（

＜0.05）；HE染色结果显示模型组大鼠心肌组织内血管充血，淋巴细胞浸润，心肌细胞轻微水肿。与模型组比较，加味涤痰汤组大鼠血清CK、CK-MB、LDH、MDA下降，GSH表达和组织铁含量升高，心肌组织Keap1、Acsl4蛋白和mRNA表达降低，Nrf2、Gpx4蛋白和mRNA表达升高（

＜0.05）；HE染色显示心肌细胞病理形态有所改善。

结论

加味涤痰汤能有效改善慢性间歇性低氧过程中氧化应激对大鼠心脏造成的损伤，其机制可能是通过影响Keap1-Nrf2通路介导的铁死亡而发挥作用。

Abstract

Objective

To investigate the effect of

Modified Ditan Decoction

（加味涤痰汤， MDD） on myocardial injury in chronic intermittent hypoxia model rats， and to explore the possible mechanism.

Methods

Thirty SD rats were randomly divided into normal group， model group， and MDD group， with 10 rats in each group. The rats in the model group and the MDD group were placed in a hypoxic chamber to establish a chronic intermittent hypoxia model. The rats in the MDD group was given 14.8 g/（kg·d） MDD by gavage 30 minutes before they entered the hypoxic chamer each day， while those in the normal group and the model group were given the same dose of normal saline by gavage， for 12 weeks. The serum myocardial enzyme indicators including creatine kinase （CK）， CK myocardial band （CK-MB） and lactate dehydrogenase （LDH）， oxidative stress indicators including malondialdehyde （MDA） and glutathione （GSH） as well as iron content in the tissue were measured. The protein and mRNA expressions of kelch-like ECH-associated protein 1 （Keap1）， nuclear erythroid transcription factor 2 （Nrf2）， glutathione peroxidase 4 （Gpx4）， and Acyl-CoA synthetase long-chain family member 4 （Acsl4） in the myocardial tissue were detected， and HE staining was used to observe the morphology of cardiomyocytes.

Results

Compared to those in the normal group， the serum CK， CK-MB， LDH， and MDA levels were significantly increased in the model group， and the GSH expression and iron content were significantly reduced； additionally， the protein and mRNA expressions of Keap1 and Acsl4 in myocardial tissue were increased， while those of Nrf2 and Gpx4 were reduced （

＜0.05）. HE staining showed that in the model group， there were congested blood vessels in the myocardial tissue， infiltrated lymphocytes， and slightly swollen myocardial cells. Compared to those in the model group， the serum CK， CK-MB， LDH， and MDA levels significantly decreased in the MDD group， and GSH expression and tissue iron content were significantly increased； the protein and mRNA expressions of Keap1 and Acsl4 in myocardial tissue decreased， while those of Nrf2 and Gpx4 increased （

＜0.05）. HE staining showed that the pathological morphology of cardiomyocytes was improved in the MDD group.

Conclusion

MDD can significantly improve the cardiac injury induced by oxidative stress in rats with chronic intermittent hypoxia， and its mechanism may be related to the inhibition of ferroptosis mediated by the Keap1-Nrf2 pathway.

关键词

Keywords

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Effects of Modified Ditan Decoction （加味涤痰汤） on Myocardial Tissue Injury and Keap1-Nrf2 Signaling Pathway in Chronic Intermittent Hypoxia Model Rats

DOI：10.13288/j.11-2166/r.2022.04.013

摘要

Abstract

关键词

Keywords

references