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瓜蒌薤白半夏汤通过阻断 TGF-β/Smad 信号通路防治心肌纤维化。

Gualou Xiebai Decoction prevents myocardial fibrosis by blocking TGF-beta/Smad signalling.

机构信息

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

J Pharm Pharmacol. 2013 Sep;65(9):1373-81. doi: 10.1111/jphp.12102. Epub 2013 Jul 10.

Abstract

OBJECTIVES

The present study is aimed to investigate the effect of Gualou Xiebai Decoction (GXD) ethanol extract on myocardial fibrosis and clarify the possible mechanism.

METHODS

Rats with ligated left anterior descending coronary artery were treated with GXD ethanol extract (1.14 g/kg, 2.27 g/kg, 4.53 g/kg) daily via gavage for 4 weeks. Histopathological changes and collagen distribution were evaluated by haematoxylin and eosin and Masson staining. The mRNA levels of Collagen I and Collagen III were detected by real-time PCR. The expressions of TGF-β1, TGFβ receptor (TGFβR)I, TGFβRII, P-Smad2/3 and Smad7 were determined by Western blot.

RESULTS

GXD treatment was significantly reduced the heart weight/body weight ratio (P < 0.05) as well as the left ventricle weight/body weight ratio (P < 0.05). It also significantly alleviated the degree of inflammation, decreased myocardial collagen volume fraction (P < 0.05 ∼ 0.01), together with markedly prevented the upregulations of Collagen I and Collagen III (P < 0.05 ∼ 0.01). Moreover, GXD downregulated expressions of TGF-β1, TGFβRI, TGFβRII, Smad2/3 whereas improved Smad7 expression in the myocardial fibrosis rats.

CONCLUSIONS

GXD ameliorates myocardial fibrosis induced by cardiac infarction with ligated left anterior descending coronary artery, the mechanism maybe involve in inhibiting the TGF-β1 signalling pathway.

摘要

目的

本研究旨在探讨瓜蒌薤白汤乙醇提取物对心肌纤维化的影响,并阐明其可能的作用机制。

方法

结扎大鼠左冠状动脉前降支,造模成功后,给予瓜蒌薤白汤乙醇提取物(1.14 g/kg、2.27 g/kg、4.53 g/kg)灌胃 4 周。采用苏木精-伊红(HE)和 Masson 染色评估心肌组织的病理变化和胶原分布。采用实时荧光定量 PCR 检测 Collagen I 和 Collagen III 的 mRNA 水平。采用 Western blot 检测 TGF-β1、TGFβ 受体(TGFβR)I、TGFβRII、P-Smad2/3 和 Smad7 的表达。

结果

瓜蒌薤白汤治疗可显著降低心脏重量/体重比(P<0.05)和左心室重量/体重比(P<0.05)。它还显著减轻了炎症程度,降低了心肌胶原容积分数(P<0.05∼0.01),同时显著抑制了 Collagen I 和 Collagen III 的上调(P<0.05∼0.01)。此外,瓜蒌薤白汤还下调了心肌纤维化大鼠中 TGF-β1、TGFβRI、TGFβRII、Smad2/3 的表达,同时提高了 Smad7 的表达。

结论

瓜蒌薤白汤可改善结扎左冠状动脉前降支所致心肌纤维化,其机制可能与抑制 TGF-β1 信号通路有关。

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