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没食子酸减轻横断主动脉缩窄诱导的心力衰竭小鼠模型中的肺纤维化。

Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

作者信息

Jin Li, Piao Zhe Hao, Sun Simei, Liu Bin, Ryu Yuhee, Choi Sin Young, Kim Gwi Ran, Kim Hyung-Seok, Kee Hae Jin, Jeong Myung Ho

机构信息

Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea; Jilin Hospital Affiliated with Jilin University, 4 Nanjing street, Chuanying, Jilin 132011, China.

The Second Hospital of Jilin University, Changchun, Jilin 130041, China.

出版信息

Vascul Pharmacol. 2017 Dec;99:74-82. doi: 10.1016/j.vph.2017.10.007. Epub 2017 Oct 31.

Abstract

Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis.

摘要

没食子酸是一种在茶和其他植物中发现的三羟基苯甲酸,在动物模型中可减轻心脏肥大、纤维化和高血压。然而,没食子酸在心力衰竭中的作用尚不清楚。在本研究中,我们表明给予没食子酸可预防心力衰竭诱导的肺纤维化。通过超声心动图证实了在横断主动脉缩窄(TAC)手术8周后诱导的小鼠心力衰竭。用没食子酸而非呋塞米治疗2周可预防小鼠心脏功能障碍。没食子酸显著抑制TAC诱导的肺部病理变化,如肺质量增加、肺纤维化和肺泡形态受损。它还降低了纤维化相关基因的表达,包括I型和III型胶原、纤连蛋白、结缔组织生长因子(CTGF)和磷酸化Smad3。此外,它抑制了上皮-间质转化(EMT)相关基因的表达,如N-钙黏蛋白、波形蛋白、E-钙黏蛋白、SNAI1和TWIST1。我们认为没食子酸在治疗心力衰竭诱导的肺纤维化方面具有治疗潜力。

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