Effect of Modified Erchentang on Hif-1 and Sirtuins 1 in Patients with COPD

XIE Wen-ying; JI Shu; SHANG Li-zhi; XUE Hong-li; LIU Zhi-yong; ZHANG Jing; ZHAO Xian-min; LIU Xiao-hui; SUN Chun-yang; LU Chang-qing; ZHANG Miao; LIANG Juan-juan; WANG Yi

doi:10.13422/j.cnki.syfjx.2017100155

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Effect of Modified Erchentang on Hif-1 and Sirtuins 1 in Patients with COPD

更新时间：2024-01-04

- Effect of Modified Erchentang on Hif-1 and Sirtuins 1 in Patients with COPD
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 23, Issue 10, Pages: 155-162(2017)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.2017100155
  CLC： R285
- Published：2017
- 稿件说明：
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XIE Wen-ying, JI Shu, SHANG Li-zhi, et al. Effect of Modified Erchentang on Hif-1 and Sirtuins 1 in Patients with COPD[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(10): 155-162.
DOI：

XIE Wen-ying, JI Shu, SHANG Li-zhi, et al. Effect of Modified Erchentang on Hif-1 and Sirtuins 1 in Patients with COPD[J]. Chinese journal of experimental traditional medical formulae, 2017, 23(10): 155-162. DOI： 10.13422/j.cnki.syfjx.2017100155.

摘要

目的：观察二陈汤加味对慢性阻塞性肺疾病（COPD）患者的肺功能、氧化应激、缺氧诱导因子-1α（Hif-1α）及沉默信息调节因子1（Sirt1）的影响，评价二陈汤加味对COPD患者抗氧化损伤及抗炎的作用与机制。方法：选取符合纳入标准的急性加重期和稳定期COPD患者各120例，各期分成对照组和治疗组。各组均在西药治疗的基础上，治疗组给予二陈汤加味，疗程14 d。检测肺功能，测定血液酸碱度（pH），氧分压（PaO2），二氧化碳分压（PCO2），氧饱和度（SaO2）。紫外分光光度计检测血清还原型谷胱甘肽（GSH），超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量，酶联免疫吸附法（ELISA）测定血浆白细胞介素（interleukin）-6，IL-1β，肿瘤坏死因子-α（TNF-α）和C反应蛋白（CRP）含量，实时荧光定量PCR检测外周血单个核细胞（PBMCs）中Hif-1α和Sirt1 mRNA表达，ELISA法测定PBMCs中HIf-1α和Sirt1含量，荧光酶联免疫吸附法测定PBMCs中Sirt1活性。结果：急性加重期和稳定期治疗后，与对照组比较，治疗组1 s用力呼气容积（FEV1），1 s用力呼气量/用力肺活量（FVC）均显著增大（P<0.01），治疗组总有效率明显高于对照组（P<0.05），治疗组PaO2，SaO2均显著增加，PCO2显著降低（P<0.01），SOD，GSH-Px活性均显著升高（P<0.01），MDA含量显著降低（P<0.01），治疗组PBMCs中Sirt1 mRNA表达，Sirt1含量及其活性均明显增加（P<0.05，P<0.01），IL-1β，IL-6，TNF-α，CRP，Hif-1α含量，Hif-1α mRNA表达均明显降低（P<0.05）。结论：二陈汤加味对COPD有抗氧化损伤、抗炎作用。其机制可能为增强Sirt1基因的表达，提高Sirt1活性，抑制Hif-1α mRNA表达，减少IL-1β，IL-6，TNF-α，CRP合成与释放，以保护肺组织、改善肺功能。

Abstract

Objective: To observe the effect of modified Erchentang on lung function

oxidative stress

Hif-1α and Sirtuins1 (Sirt1) in patients with chronic obstructive pulmonary disease (COPD)

in order to evaluate the effect and mechanism of modified Erchentang on oxidative damage and anti-inflammation in patients of COPD. Method: A multicenter

randomized single blind and placebo-controlled study was carried out. Totally 120 cases of COPD patients in acute exacerbation stage and 120 cases patients in stable stage were selected. Patients were randomly divided into modified Erchentang group and placebo-controlled group. In addition to the western medicine

modified Erchentang was additionally used in modified Erchentang group

and placebo was additionally used in control group for 14 days. The lung function was detected

and pH

PaO2

PCO2 and SaO2were measured. Ultraviolet spectrophotometer was used to detect glutathione(GSH)

superoxide dismutase(SOD) and malondialdehyde(MDA). Euzyme-linked immunosorbent assay (ELISA) was used to determine the levels of interleukin (IL)-6

IL-1β

tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) in patients plasma of all groups before and after treatment. Real-time PCR was used to determine the expressions of Hif-1α and Sirt-1 mRNA

and content of Hif-1α and Sirt-1 in PBMCs was measured by ELISA method. The activity of Sirt1 was determinate by Enzyme-linked immune fluorescence. Result: Compared with the control group

forced expiratory volume in one second (FEV1)

forced expiratory volume in one second to forced vital capacity ratio (FEV1%)

PaO2

SaO2

SOD

GSH-Px

the activity of Sirt1 in treatment group were higher significantly. However

the levels of PCO2

MDA

IL-1β

IL-6

TNF-α and CRP in plasma

the total number of neutrophils

inflammatory cells

the expressions of Hif-1α mRNA and the content of Hif-1α were significantly lower in COPD treatment group with modified Erchentang in acute exacerbation and stable stages than those in control group. Conclusion: Modified Erchentang has anti-oxidative damage and anti-inflammatory effect on COPD. It may weaken the oxidation damage

reduce levels of inflammation medium IL-1β

IL-6

TNF-α and CRP

prevent inflammatory progress

adjust the expressions of Hif-1α and Sirt-1 mRNA

so as to treat COPD and improve the structure and function of the lung through multiple targets and in multiple ways.

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Related Institution

Henan Province Hospital of Traditional Chinese Medicine（TCM），the Second Affiliated Hospital of Henan University of TCM

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Xiyuan Hospital， China Academy of Chinese Medical Sciences

Beijing University of Chinese Medicine

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