OBJECTIVETo observe the effects of warming yang method, nourishing yin method, activating blood method, and the combined treatment method on the ventricular remodeling (VR) and the heart function of heart failure (HF) rats of Shen-yang deficiency syndrome (SYDS).

METHODSThe Sprague-Dawley (SD) HF rat model of SYDS was established by continuously intravenous dripping adriamycin after economizing bilateral thyroid tissues. Rats were then randomly divided into the model group (administered with normal saline at the daily dose of 6 mL/kg by gastrogavage), the warming yang group (administered with Wenyang Jianxinling Extractum at the daily dose of 6 mL/kg by gastrogavage), the activating blood group (administered with Ligusticum Wallichii and Salvia Miltiorrhiza Extractum at the daily dose of 6 mL/kg by gastrogavage), the nourishing yin group (administered with Radix Ophiopogonis and Rhizoma Anemarrhenae Extractum at the daily dose of 6 mL/kg by gastrogavage), and the combined treatment group (administered with Yin-Yang Supplementing Extractum at the daily dose of 6 mL/kg by gastrogavage), 10 in each group. Another 10 SD rats were taken as the normal control group. They ate food and drank water freely. All rats were intervened for four successive weeks. The left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure of development ( +dp/dtmax), and maximal rate of left ventricular pressure of decline (-dp/dtmax) were observed. The systolic blood pressure (SBP) and the diastolic blood pressure (DBP) were determined. The mean arterial pressure (MAP) was calculated. The heart rate (HR) was recorded. Then all rats were killed and their hearts were taken out to weigh the heart mass (HM), the left ventricular mass (LVM), the right ventricular mass (RVM). The heart mass index (HMI) and the left ventricular mass index (LVMI) were calculated. The mRNA expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP1) in the myocardium were detected using RT-PCR. The serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), MMP-9, and TIMP-1 were assayed by double antibody sandwich ELISA.

RESULTSCompared with the normal control group, HR, LVEDP, HM, LVM, HMI, RVM, LVMI, NT-proBNP, MMP-9, and MMP-9 mRNA significantly increased, but SBP, DBP, MAP, LVSP, +/- dp/dtmax, TIMP-1, and TIMP-1 mRNA significantly decreased in the model group with statistical difference (P<0.05). Compared with the model group, SBP and DBP, +/-dp/dtmax increased,while LVEDP, NT-proBNP, and MMP-9 decreased in the warming yang group. HR, LVEDP, HM, LVM, HMI, RVM, LVMI, MMP-9 mRNA, NT-proBNP, and MMP-9 significantly decreased, while TIMP-1 mRNA increased in the activating blood group. HR, LVEDP, +/- dp/dtmax, LVMI, NT-proBNP, and MMP-9 decreased, while TIMP-1 increased in the combined treatment group, showing statistical difference (P<0.05). Compared with the warming yang group, SBP and +dp/dtmax decreased in the nourishing yin group; HR and MMP-9 mRNA decreased in the activating blood group, HR decreased in the combined treatment group, all showing statistical difference (P<0.05). There was no statistical difference in the rest indices (P>0.05).

CONCLUSIONActivating blood method and combined treatment method could regulate the expressions of MMP-9 and TIMP1 mRNA of HF rats of SYDS, effectively ameliorate the VR, and improve the HF.