Protective role of berberine in isoprenaline-induced cardiac fibrosis in rats

Yan Che,Ya-Ge Jin,Yuan Yuan,Sha-Sha Wang,Qing-Qing Wu,Di-Fei Shen,Zhao-Peng Wang

doi:10.1186/s12872-019-1198-9

Yan Che, Ya-Ge Jin + Show 5 more

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https://doi.org/10.1186/s12872-019-1198-9

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Abstract

BackgroundCardiac fibrosis is a crucial aspect of cardiac remodeling that can severely affect cardiac function. Cardiac fibroblasts surely influence this process. Besides, macrophage plays an essential role in cardiac remodeling after heart injury. However, whether macrophage influence fibroblasts remain a question worth exploring. This study aimed to define the role of berberine (BBR) on isoprenaline (ISO)-induced cardiac fibrosis in an in vivo rat model and try to figure out the mechanism in vitro study.MethodsThe Sprague-Dawley rats were divided into five groups: control group, ISO-treated group, and ISO + BBR (10 mg/kg/d, 30 mg/kg/d, and 60 mg/kg/d orally)-pretreatment groups. Fibrosis was induced by ISO administration (5 mg/kg/d subcutaneously) for 10 days. One day after the last injection, all of the rats were sacrificed. Using picrosirius red (PSR) straining, immunohistochemistry, immunofluorescence, flow cytometry, western blot, RT-qPCR and cell co-culture, we explored the influence of pretreatment by BBR on ISO-induced cardiac fibrosis.ResultsOur results showed that BBR pretreatment greatly limited ISO-induced cardiac fibrosis and dysfunction. Moreover, BBR administration reduced macrophage infiltration into the myocardium of ISO-treated rats and inhibited transforming growth factor (TGF)-β1/smads signaling pathways in comparison to that seen in the ISO group. Besides, in vitro study showed that BBR-pretreatment reduced ISO-induced TGF-β1 mRNA expression in macrophages and ISO stimulation of macrophages significantly increased the expression of fibrotic markers in fibroblasts, but BBR-pretreatment blocked this increase.ConclusionOur results showed that BBR may have a protective role to cardiac injury via reducing of macrophage infiltration and forbidding fibroblasts transdifferent into an ‘activated’ secretory phenotype, myofibroblasts.

Highlights

Cardiac fibrosis is a crucial aspect of cardiac remodeling that can severely affect cardiac function
The ISO treated rats showed higher heart weight to body weight ratios (HW/Heart weight to body weight ratios (BW)) compared to that seen in the control rats; this increase was ameliorated by pretreatment with BBR (Table 1)
Berberine reduced Transforming growth factor-β1 (TGF-β1)/smads signaling pathway in ISO-induced rat heart we investigated whether signal transduction via the transforming growth factor (TGF)-β1/smads signaling pathway was relevant to the actions of BBR in ISO-induced cardiac fibrosis

Summary

Introduction

Cardiac fibrosis is a crucial aspect of cardiac remodeling that can severely affect cardiac function. Macrophage plays an essential role in cardiac remodeling after heart injury. Whether macrophage influence fibroblasts remain a question worth exploring. This study aimed to define the role of berberine (BBR) on isoprenaline (ISO)-induced cardiac fibrosis in an in vivo rat model and try to figure out the mechanism in vitro study. The development of new therapies targeting cardiac fibrosis may limit cardiac remodeling and the subsequent development of heart failure. The activation of cardiac fibroblast transdifferentiation and the subsequent extracellular matrix deposition are key cellular events that drive the fibrotic response in the course of cardiac stress. It is worth noting that transforming growth factor (TGF)-β-producing inflammatory cells play a crucial role in this process [1]. The administration of ISO to induce myocardial injury in Sprague-Dawley (SD) rats in the experimental setting has been commonly used in previous studies as to

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