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Syringa pinnatifolia Hemsl (SP), one of the most representative Mongolian medicine has been widely used for treatment of “He-Yi” related diseases especially coronary heart disease in Inner Mongolian religion of China for hundreds of years. Our previous study has demonstrated that SP possessed the cardio-protective effects against acute myocardial infarction (AMI) by pretreatment in mice underlying an anti-inflammation mechanism through COXs pathway. The present study is to investigate the cardio-protective effect of a major fraction (M) in mice, which obtained phytochemically from total extract of SP with 81 % of total weight, and explore its mechanism of action in anti-apoptosis pathway mediated by P53.
Left anterior descending (LAD) artery was ligated to produce myocardial infarction to evaluate the anti-myocardial ischemia effect of M. Male ICR mice were randomly divided into six groups (n = 10 per group): a sham group, a model group, group treated with M at three dosages (17 mg/kg, 33 mg/kg, and 65 mg/kg, intragastrically), and a positive control group (captopril, 20 mg/kg, intragastrically). Heart function was determined mainly by ejection fraction (EF) and fractional shortening (FS) that were gained through echocardiography. In serum, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and hypersensitive C-reactive protein (hs-CRP) were detected as indicated components in AMI. Levels of protein in the heart tissue related to apoptosis, such as P53, bax, and cytochrome C, were tested by western-blot. And mRNA expressions of P53 was detected through RT-PCR. Moreover, infiltration of inflammatory cells of infarction area edge and cardiomyocyte necrosis were observed by HE staining.
Compared with total extract of SP, M showed equal, even slightly better efficacy that improved heart function by increasing values of EF and FS. The levels of serum CK-MB, LDH, and hs-CRP decreased obviously, and the same effect observed also in captopril group. Western-blot analysis showed decreased expression of protein related to P53 pathway, including P53, bax, caspase-9, caspase-3, and cytochrome C. HE staining showed that there was an obvious effect on reducing infiltration of inflammatory cells and necrosis of cardiomyocyte after administration of M compared with model group.
The major fraction of SP extract showed efficacy of anti-myocardial ischemia by down-regulating mRNA and protein expressions related to P53 pathway. These results validated the determined effect of SP in AMI through anti-apoptosis way, which brought evidence for SP in treating coronary heart disease in clinical.