Sirt1 Ischemic Myocardial Apoptosis Signal Transduction Mechanism And Blood Stasis And Students New Law Intervention Study

BackgroundIschemic heart disease has become one of major diseases which threatened human health, it characterized by irreversible myocardial systolic and diastolic function with complete apoptosis. Studies have shown that, SIRT1-mediated signal transduction pathway is closely related to the pathogenesis of IHD, it can extend the life of cell, and to through the control of its downstream genes the signal transduction pathway can Inhibit the cell apoptosis. Resveratrol is the sensitizer and L-NAME is inhibitors. Meanwhile, the mechanism of the transduction pathway of the treatment of ischemic heart disease is coincide with the, "Qu yu sheng xin" method in Chinese medicine. At present, Xuefuzhuyu capsule as a typical clinical application of "Qu yu sheng xin" method in Chinese medicine, it has clear effective. Therefore, the discussion of the mean mechanisms of which SIRT1 signal transduction controlled by Chinese medicine for ischemic heart disease treatment can possible develop a new field for Chinese medicine treatment of ischemic heart disease.ObjectiveFirst of all, to clarify the mechanism of apoptosis signal transduction of SIRT1-mediated in Ischemic myocardial cells of IHD, and find out the reason that ischemic heart disease turn to heart failure or arrhythmia.The second, to Discuss the effect of the intervention that Xuefuzhuyu capsule drive to the SIRT1-mediated suppression of apoptosis signal transduction pathway, and make the objective basis for the clinical application of Chinese medicine on Xuefuzhuyu capsule.The third, to find evidence that Xuefuzheyu capsule could be a new sensitizer to the SIRTlinhibition-apoptosis pathway, and make a further application for Xuefuzhuyu capsule, while provide a new research targets of Chinese medicine in preventing ischemic heart disease.Materials and Methods80 healthy adult Wister rats were randomly divided into 8 groups, so as normal group, sham operation group, ischemia group, large dose of Xuefuzhuyu capsule group, medium dose of Xuefuzhuyu capsule group, low dose of Xuefuzhuyu capsule group, resveratrol group and L-NAME group, 10rats in each group. Except the normal group and the sham operation group, the remaining rats were prepared to ligate the left coronary artery to make the model of myocardial ischemia, and after 30 min then release the ligature. The Sham group only wear line without ligation. The resveratrol group were administered intravenously sublingual 15min before ischemia. The L-NAME group were intraperitoneal injected at 1 day before modeling, 2mg/only,1 time/day. The Xuefuzhuyu capsule large, medium, low dose group were given 10,20,30 mg/kg Xuefuzhuyu capsule after the success of the modeling, gavage for 4 weeks. And the normal group, the sham operation group, and the ischemia reperfusion group were fed by the same volume of saline, gavage for 4 weeks too. Remove the rats'hearts by the end of the experiment, and collected the specimens for the electron microscope and the polymerase chain reaction (PCR) test. Then observed the myocardial cells and tissue by electron microscopy and took photos, meanwhile, detected the quantitative PCR test. Analysis the experimental data by using the statistical package SPSS 19.0 to statistic.Results1.The result of the electron microscope:in morphology, it had significantly different between the 8 different groups.2.The result of the PCR test:the expression of SIRT1, P53,(NF)-κB, FOXO1, FOXO3, FOXO4 between normal group, sham operation group, large dose of Xuefuzhuyu capsule group were no significant difference, (P>0.05) while the expression between ischemia group and L-NAME group were no significant difference, (P>0.05). But to contrast normal group, sham operation group, large dose of Xuefuzhuyu capsule group with ischemia group and L-NAME group relatively, the expression of SIRT1, FOXO1, FOXO3, FOXO4 were significant differences, (p<0.05). The expression of medium dose of Xuefuzhuyu capsule group and low dose of Xuefuzhuyu capsule group were lower than large dose of Xuefuzhuyu, but better than the ischemic group and L-NAME group.Conclusionl.The SIRT1-mediated signal transduction pathway can effectively control the downstream genes such as P53, (NF)-κB, FOXO1, FOXO3, FOXO4, etc. It also could enhance these genes'expression, thereby inhibiting apoptosis of myocardial cells and reduce the number of dead cells of myocardium and improve cardiac function, which can reduce reperfusion injury of ischemic heart disease, heart failure and cardiac arrhythmias.2.The SIRT1 signal transduction pathway and the Chinese "Qu yu sheng xin" method for the treatment of ischemic heart disease share a common mechanism of action and targets.3.As the representative prescription for the "Qu yu sheng xin" method, Xuefuzhuyu capsule could be probably applicated as the sensitizer for SIRT1 inhibits-apoptosis pathway in further future, while it provide a new research targets of preventing ischemic heart disease by Chinese medicine.