Effect of Shenqi Yangxin decoction on high mobility group box 1 and inflammatory signal pathway in a rat model of dilated cardiomyopathy.

OBJECTIVE: To investigate the effects of Shenqi Yangxin decoction (SQYXD) on heart function in a rat model of dilated cardiomyopathy (DCM) and its potential mechanisms. METHODS: Sprague-Dawley rats were randomly divided into normal (10 rats) and DCM (150 rats) groups. DCM was induced by an intraperitoneal injection of adriamycin. Then, DCM baseline group was randomly selected sixteen DCM rats. The remaining DCM rats were randomly divided into DCM control, perindopril, metoprolol, and SQYXD groups. Cardiac function and histological analysis plus biochemical measurement of serum levels of brain natriuretic peptide (BNP), and inflammatory factors were measured. The mRNA and protein expression levels of high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR-4), receptor for advanced glycation end products (RAGE), and nuclear factor-¦ÊB (NF-¦ÊB) were determined. Myocardial metabolism imaging was performed on the normal, SQYXD and DCM control groups to evaluate the effectiveness of treatments. RESULTS: Rats in the DCM control group exhibited dilated left ventricular diameter, impaired cardiac function, disorganized sarcomere, impaired glucose metabolism, increased heart weight index, and increased levels of BNP, which were improved by treatment with SQYXD. In addition, hearts from rats in the DCM baseline group exhibited significantly higher levels of HMGB1, TLR-4, RAGE, NF-κB, tumor necrosis factor-α, interleukin-1, interleukin-6, interleukin-10, compared with the normal group. Interestingly, the mRNA level of HMGB1 in the DCM baseline group was positively correlated with that of TLR-4, RAGE, NF-κB, BNP, and LVEDD, but negatively correlated with LVEF. SQYXD inhibited the upregulation of HMGB1 expression and its downstream inflammatory factors. CONCLUSION: Shenqi Yangxin decoction effectively reduced the dilated left ventricular diameter and improved heart function in dilated cardiomyopathy. The mechanisms underlying the action on DCM involve regulating the gene and protein expression of HMGB1 and its inflammatory signal pathways in the DCM rat model.

Developing a rat model of dilated cardiomyopathy with improved survival.

To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function (all P<0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased (P<0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and 18F-fluoro-deoxyglucose-positron emission tomography (18FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles (LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate.