黄芪甲苷对特发性肺纤维化自噬活性作用及PI3K/Akt/mTOR信号调控的影响

被引：115

作者：

徐昌君 ^{[1
]}

王鹏飞 ^{[1
]}

刘杨 ^{[1
]}

黄雅薇 ^{[2
]}

杨长福 ^{[1
]}

赵宗江 ^{[2
]}

机构：

[1] 贵阳中医学院

[2] 北京中医药大学

来源：

中国实验方剂学杂志 | 2017年 / 23卷 / 18期

关键词：

特发性肺纤维化; 黄芪甲苷; 自噬; 上皮间质转分化; 磷酯酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/mTOR信号;

D O I：

暂无

中图分类号：

R285.5 [中药实验药理];

学科分类号：

100806 [中药药理学];

摘要：

目的:研究黄芪甲苷对特发性肺纤维化自噬活性影响及其磷酯酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/mTOR信号的调控作用,探讨黄芪的抗肺纤维化机制。方法:c57bl/6小鼠分为假手术组、模型组、黄芪甲苷低、中、高剂量组、泼尼松组。博莱霉素(BLM)10 mg·kg-1诱导建立肺纤维化动物模型,以黄芪甲苷低、中、高剂量(25,50,100 mg·kg-1)干预,分别于3,7,14,28 d取材,进行苏木素-伊红(HE)染色观察肺组织形态变化,马松(Masson)三色染色、羟脯氨酸测定观察胶原表达水平,免疫组化及蛋白质免疫印迹(Western bolt)分析自噬标记蛋白和PI3K/Akt/mTOR信号蛋白表达水平。结果:与空白组比较,模型组肺组织炎症反应明显、胶原蛋白显著增加(P<0.01),PI3K/Akt/mTOR信号增强,自噬活性下降,与模型组比较,黄芪甲苷中、高剂量明显抑制肺组织炎症反应,下调转化生长因子-β1(TGF-β1)(P<0.01)和胶原蛋白(P<0.05)表达,提高LC3Ⅱ/Ⅰ和(beclin-1)表达(P<0.05),减少p62积累(P<0.05),同时抑制PI3K,Akt,mTOR磷酸化水平(P<0.05),减少ɑ-平滑肌动蛋白(ɑ-SMA)而提高E-钙黏素(E-cadherin)表达(P<0.01)。结论:黄芪甲苷通过抑制肺组织炎性反应、下调TGF-β1表达,抑制PI3K/Akt/mTOR信号增强肺组织细胞自噬活性,阻止上皮间质转分化(EMT)过程。

引用

页码：75 / 82

页数：8

共 21 条

[1]

mTOR Overactivation and Compromised Autophagy in the Pathogenesis of Pulmonary Fibrosis..[J].Yao-Song Gui;Lianmei Wang;Xinlun Tian;Xue Li;Aiping Ma;Weixun Zhou;Ni Zeng;Ji Zhang;Baiqiang Cai;Hongbing Zhang;Jing-Yu Chen;Kai-Feng Xu.PLoS ONE.2017, 9

[2]

Inhibitory Effects of Astragaloside IV on Bleomycin-Induced Pulmonary Fibrosis in Rats Via Attenuation of Oxidative Stress and Inflammation [J].

Yu, Wei-Na ;

Sun, Li-Feng ;

Yang, Hua .

INFLAMMATION, 2016, 39 (05) :1835-1841

[3]

Pirfenidone in the treatment of idiopathic pulmonary fibrosis: an evidence-based review of its place in therapy [J].

Margaritopoulos, George A. ;

Vasarmidi, Eirini ;

Antoniou, Katerina M. .

CORE EVIDENCE, 2016, 11 :11-22

[4]

KCa3.1 mediates dysfunction of tubular autophagy in diabetic kidneys via PI3k/Akt/mTOR signaling pathways [J].

Huang, Chunling ;

Lin, Mike Z. ;

Cheng, Delfine ;

Braet, Filip ;

Pollock, Carol A. ;

Chen, Xin-Ming .

SCIENTIFIC REPORTS, 2016, 6

[5]

Berberine inhibits Smad and non-Smad signaling cascades and enhances autophagy against pulmonary fibrosis [J].

Chitra, Palanivel ;

Saiprasad, Gowrikumar ;

Manikandan, Ramar ;

Sudhandiran, Ganapasam .

JOURNAL OF MOLECULAR MEDICINE-JMM, 2015, 93 (09) :1015-1031

[6]

The Role of TGF-β Receptors in Fibrosis..[J].Nakerakanti Sashidhar;Trojanowska Maria.The open rheumatology journal.2012, 1

[7]

Hepatocyte growth factor attenuates renal fibrosis through TGF-β1 suppression by apoptosis of myofibroblasts [J].

Iekushi, Kazuma ;

Taniyama, Yoshiaki ;

Azuma, Junya ;

Sanada, Fumihiro ;

Kusunoki, Hiroshi ;

Yokoi, Toyohiko ;

Koibuchi, Nobutaka ;

Okayama, Keita ;

Rakugi, Hiromi ;

Morishita, Ryuichi .

JOURNAL OF HYPERTENSION, 2010, 28 (12) :2454-2461

[8]

Atrial fibrosis and atrial fibrillation: The role of the TGF-β 1 signaling pathway.[J].Felix Gramley;Johann Lorenzen;Eva Koellensperger;Klaus Kettering;Christian Weiss;Thomas Munzel.International Journal of Cardiology.2009, 3

[9]

TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease..[J].Willis Brigham C;Borok Zea.American journal of physiology. Lung cellular and molecular physiology.2007, 3

[10]

Induction of Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells by Transforming Growth Factor-β1.[J].Brigham C. Willis;Janice M. Liebler;Katherine Luby-Phelps;Andrew G. Nicholson;Edward D. Crandall;Roland M. du Bois;Zea Borok.The American Journal of Pathology.2005, 5

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