Objectives The Xuefuzhuyu capsule is used for the treatment of ischaemic heart disease in China. Evidences have demonstrated that Xuefuzhuyu capsule could protect cardiomyocytes from injury induced by ischaemia, but molecular mechanism underlying this protective effect are still unclear. This study was aimed to investigate potential molecular mechanism by which the protective effect might attributed to an anti-apoptotic effect of Xuefuzhuyu capsule involved in SIRT1 signal transduction pathway using rat myocardial ischaemia injury model.
Methods Sprague-Dawley (SD) rats subjected to left anterior descending (LAD) coronary artery ligation. Those rats were divided into 8 groups, including the normal group, the sham operation group, the ischaemia group, the large-dose of Xuefuzhuyu group, the middle-dose of Xuefuzhuyu group, the Low-dose of Xuefuzhuyu group, the Res group and the L-NAME group. The effect on cell apoptosis of Xuefuzhuyu capsule was evaluated under microscope. The mRNA expression levels of SIRT1 as well as its downstream target genes were detected in real time PCR assay.
Results 1) Based on shape parameters of the myocardial tissue in the image of electron micrograph, it seemed that myocardial ischaemia caused the mitochondrial swelling and the cardiac sarcomere striped fuzzy. In Xuefuzhuyu groups and Res group the changes of the myocardial tissue were improved significantly. 2) There are significant difference in the expression levels of SIRT1, P53, nf-kB, FOXO1, FOXO3, FOXO4 among low, middle, and high-dose of Xuefuzhuyu group, ischaemia group, Resveratrol group, L-NAME group, as well as normal group (p < 0.05). The expression levels of SIRT1 in the high-dose of Xuefuzhuyu group and Res group are significantly higher than which in the low and middle-dose of Xuefuzhuyu group. The expression levels of P53, nf-kB, FOXO1, FOXO3, and FOXO4 in the high-dose of Xuefuzhuyu group and Res group are significantly lower as compared to the low and middle-dose of Xuefuzhuyu group with p value less than 0.05. The expression level of SIRT1 in the normal group is the highest and in the L-NAME group is the lowest. P53, nf-kB, FOXO1, FOXO3, and FOXO4 express higher in L-NAME group than Xuefuzhuyu groups.
Conclusions Results of this study demonstrate that the Xuefuzhuyu capsule might has the same pharmacological effect as Res in protecting myocardial cells and reducing myocardial injury though SIRT1 signaling pathway might be its possible mechanism.