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补肺汤通过抑制MAPK/AP-1信号通路和调节γ-GCS减轻慢性阻塞性肺疾病的氧化应激状态。

Recuperating Lung Decoction Attenuates the Oxidative Stress State of Chronic Obstructive Pulmonary Disease by Inhibiting the MAPK/AP-1 Signal Pathway and Regulating -GCS.

作者信息

Li Chunlei, Shi Qi, Yan Yue, Kong Yanhua, Meng YanYan, Wang Tiezhu, Zhang Xing, Bao Haipeng, Li Youlin

机构信息

Beijing University of Chinese Medicine, Beijing 100029, China.

The 2nd Pulmonary Department of TCM, The Key Institute of State Administration of Traditional Chinese Medicine (Pneumonopathy Chronic Cough and Dyspnea), Beijing Key Laboratory (No. BZ0321), China-Japan Friendship Hospital, Beijing 100029, China.

出版信息

Evid Based Complement Alternat Med. 2017;2017:9264914. doi: 10.1155/2017/9264914. Epub 2017 Mar 20.

Abstract

. To evaluate the effects of Recuperating Lung Decoction (RLD) on the indices of oxidative stress in a rat model of COPD and detect the indices of the MAPK/AP-1/-GCS signal pathway for a further survey of the possible targeting site of RLD. . The rats of COPD were treated with RLD. The protein levels of glutathione (GSH), oxidized glutathione (GSSG), 8-hydroxy-2-deoxyguanosine (8-OHdG), and 4-hydroxynonenal (4-HNE) were measured. In addition, the levels of key signaling molecules (extracellular signal-regulated kinases [ERK], the c-jun N-terminal kinase [JNKs signal pathway], and p38 MAP kinase [p38MAPK], AP-1 proteins [C-fos, C-jun], and -glutamyl-cysteine synthetase [-GCS-h]) of the MAPK/AP-1/-GCS-h signal pathway were assessed. . After treatment, the protein level of GSH and the ratio of GSH/GSSG were increased and the amounts of 8-OHdG and 4-HNE were decreased significantly in lung tissues when compared with the nontreated COPD group. Further results showed that the RLD could effectively inhibit the MAPK pathway by inactivation of p38MAPK and ERK and could also downregulate the AP-1 and the -GCS-h genes expressions in both protein and mRNA levels. . RLD might improve the state of oxidative stress by downregulation of the expression of -GCS-h gene by inhibition of the MAPK/AP-1 pathway, thereafter enhancing the ability of antioxidation in COPD.

摘要

观察补肺汤(RLD)对慢性阻塞性肺疾病(COPD)大鼠模型氧化应激指标的影响,检测丝裂原活化蛋白激酶/活化蛋白-1/γ-谷氨酰半胱氨酸合成酶(MAPK/AP-1/-GCS)信号通路指标,进一步探寻补肺汤可能的作用靶点。将COPD大鼠用补肺汤治疗。检测谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)、8-羟基-2'-脱氧鸟苷(8-OHdG)和4-羟基壬烯醛(4-HNE)的蛋白水平。此外,评估MAPK/AP-1/-GCS-h信号通路关键信号分子(细胞外信号调节激酶[ERK]、c-jun氨基末端激酶[JNKs信号通路]、p38丝裂原活化蛋白激酶[p38MAPK]、AP-1蛋白[C-fos、C-jun]和γ-谷氨酰半胱氨酸合成酶[γ-GCS-h])的水平。治疗后,与未治疗的COPD组相比,肺组织中GSH蛋白水平及GSH/GSSG比值升高,8-OHdG和4-HNE含量显著降低。进一步结果显示,补肺汤可通过使p38MAPK和ERK失活有效抑制MAPK通路,还可在蛋白和mRNA水平下调AP-1和γ-GCS-h基因表达。补肺汤可能通过抑制MAPK/AP-1通路下调γ-GCS-h基因表达,从而改善氧化应激状态,增强COPD的抗氧化能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a68/5376952/6a5f235beb6a/ECAM2017-9264914.001.jpg

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