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补肺益肾方 III 联合电针对慢性阻塞性肺疾病大鼠炎症反应的抑制作用及其调控 SIRT1/NF-κB 信号通路的研究

Effective-Component Compatibility of Bufei Yishen Formula III Combined with Electroacupuncture Suppresses Inflammatory Response in Rats with Chronic Obstructive Pulmonary Disease via Regulating SIRT1/NF-B Signaling.

机构信息

Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China.

Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province & Education Ministry of P.R. China, Zhengzhou, Henan 450046, China.

出版信息

Biomed Res Int. 2022 May 9;2022:3360771. doi: 10.1155/2022/3360771. eCollection 2022.

Abstract

OBJECTIVE

To explore more efficient treatments for chronic obstructive pulmonary disease (COPD), effective-component compatibility of Bufei Yishen formula III (ECC-BYF III) and electroacupuncture were tested on rats with COPD, and silent information regulator transcript-1 (SIRT1)/nuclear factor-kappaB (NF-B) signaling was further investigated to interpret the therapy.

METHODS

In total, 70 rats were randomly divided into control (Control), model (Model), aminophylline (APL), ECC-BYF III, electroacupuncture (EA), ECC-BYF III+EA, and sham electroacupuncture (SA) groups. Cigarette smoke exposure combined with repeated bacterial infections was used to establish COPD models in 1-12 weeks. From 13 to 20 weeks, the ECC-BYF III and APL groups received corresponding drugs; the EA group received electroacupuncture therapy, wherein Dazhui (GV 14), Feishu (BL 13), and Shenshu (BL 23) points were selected; the ECC-BYF III+EA group received ECC-BYF III intragastrically combined with electroacupuncture; and the SA group received simulated electroacupuncture (nonacupoint). Pulmonary function, pulmonary histopathology, the expressions of SIRT1/NF-B signaling, and inflammation-related mRNA and protein were detected.

RESULTS

Significant deterioration was observed in pulmonary function and pulmonary histopathology in rats with COPD ( < 0.01), and inflammatory state was illustrated by increased levels of interleukin- (IL-) 6 and tumor necrosis factor alpha (TNF-) and decreased levels of IL-10 ( < 0.01). After the intervention of APL, ECC-BYF III, EA, and ECC-BYF III+EA, both pulmonary function and pulmonary histopathology were improved ( < 0.05 and < 0.01), whereas the levels of IL-6 and TNF- were decreased and IL-10 was increased ( < 0.05 and < 0.01). Additionally, the mRNA expressions of IL-6, TNF-, NF-B, and acetylated NF-Bp65 (Ac-NF-B) were noted to decrease, and SIRT1 and IL-10 were increased ( < 0.05 and < 0.01); the protein expression of SIRT1 was upregulated, and NF-Bp65 and Ac-NF-B were downregulated ( < 0.05 and < 0.01). The effect of ECC-BYF III+EA was better in terms of improving pulmonary function and alleviating inflammation than that of the other treatment groups ( < 0.01 and < 0.05).

CONCLUSIONS

ECC-BYF III, electroacupuncture, and their combination can suppress inflammation, among which the combination therapy has been proven to be the most effective treatment, and the mechanism may be involved in activating SIRT1/NF-B signaling.

摘要

目的

为探索慢性阻塞性肺疾病(COPD)的更有效治疗方法,考察补肺益肾方Ⅲ号(ECC-BYF III)有效部位配伍及电针对 COPD 大鼠的作用,并进一步探讨沉默信息调节因子转录-1(SIRT1)/核因子-κB(NF-κB)信号通路,阐释其作用机制。

方法

70 只大鼠随机分为对照组(Control)、模型组(Model)、氨茶碱组(APL)、ECC-BYF III 组、电针组(EA)、ECC-BYF III+EA 组和假电针组(SA)。112 周采用香烟熏吸联合重复细菌感染法建立 COPD 模型,1320 周 ECC-BYF III 和 APL 组分别灌胃相应药物,EA 组电针刺激“大椎”“肺俞”“肾俞”穴,ECC-BYF III+EA 组电针联合灌胃,SA 组模拟电针(非穴位)。检测大鼠肺功能、肺组织病理学改变,检测 SIRT1/NF-κB 信号通路及其相关炎症因子 mRNA 和蛋白的表达。

结果

COPD 大鼠肺功能和肺组织病理学明显恶化( < 0.01),炎症状态表现为白细胞介素-(IL-)6 和肿瘤坏死因子-α(TNF-α)水平升高,IL-10 水平降低( < 0.01)。APL、ECC-BYF III、EA 和 ECC-BYF III+EA 干预后,大鼠肺功能和肺组织病理学均有改善( < 0.05 和 < 0.01),IL-6 和 TNF-α水平降低,IL-10 水平升高( < 0.05 和 < 0.01)。同时,IL-6、TNF-、NF-κB、乙酰化 NF-κBp65(Ac-NF-κB)mRNA 表达降低,SIRT1 和 IL-10 表达升高( < 0.05 和 < 0.01);SIRT1 蛋白表达上调,NF-κBp65 和 Ac-NF-κB 蛋白表达下调( < 0.05 和 < 0.01)。ECC-BYF III+EA 组在改善肺功能、减轻炎症方面的效果优于其他治疗组( < 0.01 和 < 0.05)。

结论

ECC-BYF III、电针及其联合应用均可抑制炎症,其中联合治疗效果最佳,其作用机制可能与激活 SIRT1/NF-κB 信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c108/9110177/8d0c9418b0ea/BMRI2022-3360771.001.jpg

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