Effects Of SXTXDW On Peripheral Microcirculation Dysfunction In Mice Subjected To Myocardial Infarction And Involved Mechanisms

In patients with AMI,the coronary microvasculature was usually injured during the initial ischemia attack process,and got worse and worse with the disease progression,which would do harm to the myocardium and lead severe damage and clinical symptoms.The potential role of coronary microcirculation dysfunction(CMD)in cardiovascular was neglected for decades.A lot of invasive and non-invasive assessment of coronary artery function gave us plenty of information about CMD and inspired us to get a clear image behind it.With more and more date available from not only the basic research but also clinical trials,the importance of coronary microcirculation dysfunction has drawn great importance.Therefore,to explore the pathogenesis of coronary microcirculation dysfunction is the key to implement effective and safe intervention in clinic.Shexiang Tongxin Dropping Pill has been clinically proved to be effective in improving the symptoms of patients with CMD,but the mechanism was still elusive.Our study would try to uncover whether Shexiang Tongxin Dropping Pill could improve the abnormal microcirculation in the mice model and potential mechanism.Objective: To explore the protective effects and involved mechanism of Shexiang Tongxin Dropping Pill(SXTXDW)improving dysfunction of peripheral microcirculation in mice model.Methods: Fifty C57 male mice(6weeks-8weeks)were randomly divided into control group,model(MI+LPS)group,model+SXTXDW group,model+SXTXDW+PAG group and model+NaHS group.Mice in control group were given sham operation.And the other mice were given myocardial infarct(MI)operation.One week later,sham control group mice were injected intraperitoneally with normal saline,while the mice from other four groups were injected with lipopolysaccharide(LPS)in order to induce peripheral microcirculation dysfunction.Twenty-four hours later,different interventions were given to the mice in the five groups.Then the microcirculation flow velocity at different timepoints were recorded.The number of adhered leukocytes in the microcirculation,blood perfusion in the gut and the relative expression level of CD11 b and CD62 L on leukocytes were measured.At last,mice got euthanasia,and the cremaster,heart,leukocytes and aorta were collected carefully for measuring the relative expression level of CSE by qPCR and western blot.Then the adhered leukocytes in vitro,the relative expression level of FOXO1 in leukocytes and mtDNA/nDNA ratio in such cells were investigated.The area of MI was analyzed by Evan Blue injection combined TTC staining.Ultrasound and ECG were used to evaluate the heart function of such animal model.Results: Compared with mice in control group,the microcirculation flow velocity,the relative expression level of CD62 L on leukocytes and the leval of blood perfusion in the gut of mice in MI+LPS group and SXTXDW+PAG group decreased significantly(p<0.05).But the cells number of leukocytes adhered to venular wall and the relative expression level of CD11 b on leukocytes of mice in MI+LPS group and SXTXDW+PAG group increased(p<0.05).While the relative expression level of cystathionine-?-lyase(CSE)in leukocytes,heart and cremaster tissue of mice in MI+LPS group were downregulated(p<0.05).And FOXO1 level in leukocytes was up-regulated(p<0.05).The ratio of mtDNA/nDNA in leukocytes was down-regulated(p<0.05).Compared with mice in MI+LPS group,the microcirculation flow velocity and the leval of blood perfusion in the gut of mice in SXTXDW group and NaHS group increased significantly(p<0.05).While the number of leukocytes adhered to venular wall and the relative expression level of CD11 b on neutrophils decreased(p<0.05).The relative expression level of CSE in leukocytes,heart and cremaster tissue of mice in SXTXDW group were up-regulated(p<0.05).And FOXO1 level in leukocytes was down-regulated(p<0.05).The ratio of mtDNA/nDNA in leukocytes was upregulated(p<0.05).Conclusion: Shexiang Tongxin Dropping Pill could improve microvascular dysfunction in mice significantly.And hydrogen Sulfide might improve microcirculation disturbance by down-regulating FOXO1 and increasing the activity of mitochondria.