Mechanisms of Chinese Medicine Xinmailong's protection against heart failure in pressure-overloaded mice and cultured cardiomyocytes.

Mechanisms of Chinese Medicine Xinmailong's protection against heart failure in pressure-overloaded mice and cultured cardiomyocytes.

Qi Jianyong; Yu Juan; Tan Yafang; Chen Renshan; Xu Wen; Chen Yanfen; Lu Jun; Liu Qin; Wu Jiashin; Gu Weiwang; Zhang Minzhou

Scientific reports

2017

2017-02

Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML's effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14). Dynamic changes in cardiac structure and function were evaluated with echocardiography in vivo. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, AKT, GSK3beta and protein expression of GATA4 in nucleus were detected with Western blot experiment. The results showed that XML reduced diastolic thickness of left ventricular posterior wall, increased ejection fraction and fraction shortening, so as to inhibit HF at 2 weeks after TAC. Moreover, XML inhibited the phosphorylation of ERK1/2, AKT and GSK3beta, subsequently inhibiting protein expression of GATA4 in nucleus (P \textless 0.001). Together, our data demonstrated that XML inhibited the TAC-induced HF via inactivating the ERK1/2, AKT/GSK3beta, and GATA4 signaling pathway.

Animal; Animals; Cardiac/cytology/*drug effects/metabolism; Cell Nucleus/metabolism; Cell Survival/drug effects; Cells; Chinese Herbal/*administration & dosage/pharmacology; Constriction; Cultured; Disease Models; Drugs; Echocardiography; GABA Plasma Membrane Transport Proteins/*metabolism; Gene Expression Regulation/drug effects; Glycogen Synthase Kinase 3 beta/metabolism; Heart Failure/etiology/metabolism/physiopathology/*prevention & control; Humans; MAP Kinase Signaling System/drug effects; Mice; Myocytes; Pathologic; Phosphorylation; Proto-Oncogene Proteins c-akt/metabolism; Rats

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