Background and ObjectiveCoronary atherosclerotic heart disease is abbreviated as CAD.Acute myocardial infarction and sudden death are the two most dangerous clinical types of coronary heart disease.Coronary heart disease has become a serious cardiovascular disease that seriously endangers human life and health because of its high mortality and damage to the heart function.In medicine,coronary atherosclerosis and thrombosis are the pathological mechanisms of coronary heart disease.According to the theory of traditional Chinese medicine(TCM),the key pathogenesis is the insufficiency of chest Yang and the obstruction of turbid evil,and the thrombus and lipid deposition in the coronary artery belong to the blood stasis and phlegm,so the blood stasis syndrome is the most important and most common syndrome in the coronary heart disease.Panax notoginseng is one of the classic Chinese medicine for activating blood circulation and removing blood stasis.It has the characteristics of removing blood stasis and not injuring the right,and is suitable for the syndrome of deficiency and excess of chest obstruction.Panax notoginseng saponins is an important pharmacological component extracted from Panax notoginseng,and PNS is used in the clinical treatment of cardiovascular and cerebrovascular diseases,such as coronary heart disease and cerebral infarction.There are a lot of clinical studies on the treatment of coronary heart disease by PNS,but there are few studies on the study of the treatment of blood stasis syndrome of coronary heart disease by PNS and the evaluation standard of TCM syndrome effect to evaluate the improvement of blood stasis syndrome.In view of this,the first part of this study will focus on the clinical efficacy of PNS in the treatment of unstable angina pectoris of coronary heart disease with blood stasis syndrome.MicroRNA(miRNA)is an endogenous non coded small RNA that regulates cell function targeting messenger RNA(mRNA).When the expression of miRNA is abnormal,the downstream signal pathways are disorganized.This is a major cause of many diseases.Recent studies have shown that miRNA regulates the expression of a variety of important cardiovascular system proteins,participates in the physiological processes of heart development,vascular endothelial cell proliferation,myocardial repair and cardiomyocyte apoptosis,as well as the pathological processes of many cardiovascular diseases,such as coronary heart disease,myocardial infarction,myocardial hypertrophy,heart failure and heart rhythm.Disorder and so on.A number of studies have shown that miRNA let-7b plays an important role in the development of coronary heart disease and the repair of acute myocardial infarction.Let-7b is a potential biomarker for acute myocardial infarction,and let-7b may also provide new ideas for the repair and treatment of cells after myocardial infarction.The second part of this study will start with the signal pathway of let-7b and its target gene to explore whether PNS interfered with the expression of let-7b in the blood stasis syndrome of coronary heart disease,and to find the target of PNS on the blood stasis syndrome of coronary heart disease on the signal pathway of let-7b and its target gene.Method1 Clinical observation of PNS in treating coronary heart disease with unstable angina pectoris.80 patients with unstable angina pectoris blood stasis syndrome diagnosed by coronary angiography were selected by PROC PLAN program of SAS6.12 software,and the patients were randomly divided into treatment group and control group by sealed envelope according to the order of medical treatment.Two groups of patients were given anti ischemic treatment,antiplatelet therapy,hypolipidemic treatment and other conventional western medicine treatment,and symptomatic treatment according to complications.In the treatment group,40 cases were treated with Xuesaitong Capsule on the basis of routine western medicine treatment,and 40 cases in the control group were treated with Xuesaitong capsule analogue on the basis of routine western medicine treatment.The observation indexes were recorded before and after treatment:angina pectoris time,electrocardiogram,Seattle scale,blood stasis syndrome score scale,hCRP,white blood cell and liver and kidney function.Statistical analysis was performed on the observed indexes and analyzed by SPSS 19.0 software.2 The molecular mechanism of PNS intervention in let-7b of coronary heart disease with blood stasis syndrome.10 patients with unstable angina pectoris blood stasis syndrome diagnosed by coronary angiography were selected by PROC PLAN program of SAS6.12 software.The patients were randomly divided into treatment group and control group by sealed envelope according to the order of treatment.The total RNA was extracted from the peripheral venous blood under the morning fasting state.Two groups of patients were given anti ischemic treatment,antiplatelet therapy,hypolipidemic treatment and other conventional western medicine treatment,and symptomatic treatment according to complications.The treatment group was given Xuesaitong Capsule on the basis of routine treatment of Western medicine,while the control group added Xuesaitong capsule simulant on the basis of Western medicine routine treatment.After 4 weeks,peripheral venous blood was extracted again and total RNA was extracted.The target gene and related pathway of let-7b were determined by the microRNA target gene prediction software miRBase,and the real-time quantitative polymerase chain reaction was used to verify the changes of the molecules on the let-7b and related signaling pathways before and after the treatment.Statistical analysis was performed on the observed indicators and the results were analyzed.Result1 Clinical observation of PNS in treating coronary heart disease with unstable angina pectoris.After treatment,the total effective rate of angina pectoris in the treatment group was 92.5%,and the total effective rate of angina pectoris in the control group was 87.5%.The total effective rate of the treatment group was 92.5%,while that of the control group was 87.5%.The 3 dimensions of the physical activity,the stable state of angina and the condition of angina in the Seattle scale showed that the physical activity of the two groups was significantly improved(P<0.05),and the treatment group was more effective than the control group(P<0.05).The stability of angina pectoris after treatment in the two groups was significantly higher than that of the two groups.Improvement(P<0.05),but there was no significant difference between the treatment group and the control group(P>0.05),and the angina pectoris in the two groups were significantly improved(P<0.05),but there was no significant difference between the treatment group and the control group(P>0.05).The result of blood stasis syndrome score showed that the blood stasis syndrome of the two groups was significantly improved(P<0.05),and the curative effect of the treatment group was significantly higher than that of the control group(P<0.05).The results of inflammatory markers showed that the white blood cells in the treatment group decreased significantly(P<0.05),and there was no significant difference(P>0.05)in the control group after treatment(P>0.05),and the hCRP in the treatment group was significantly higher(P<0.05),and there was no significant difference between the control group(P>0.05).The results of safety indicators showed that there was no significant change in liver and kidney function and hematuria before and after treatment.There was no significant difference in Statistics(P>0.05).The basic vital signs,such as body temperature,heart rate,respiratory frequency and blood pressure,were not abnormal.2 The molecular mechanism of PNS intervention in let-7b of coronary heart disease with blood stasis syndrome.The target gene ADRB2 of let-7b was selected as a signal molecule,and two signal pathways related to ADRB2 were selected:the signal transduction pathway of adrenaline in the cardiac myocyte and the signal transduction pathway of adipocyte;and then the signal molecule ADRB2/GS/AC/cAMP/PKA/PLIN3 on the two pathways was selected as the signal molecule to be studied.The change trend of let-7b in the two groups was opposite.The let-7b of the treatment group was upregulated after PNS intervention,while the let-7b of the control group was reduced after treatment.The study found that the change trend of ADRB2 in the two groups was opposite.The ADRB2 of the treatment group was upregulated after PNS intervention,while the let-7b of the control group was reduced after treatment.The study found that the change trend of GS1 in the two groups was the opposite.The GS1 in the treatment group was up-regulated after PNS intervention,while the GS1 in the control group was downregulated after the treatment.The trend of cAMP in the two groups was the opposite.The cAMP in the treatment group was down after PNS,and the cAMP in the control group was cAMP.Up regulation after treatment;the trend of PRKACA in two groups of patients was consistent after treatment.The PRKACA in the treatment group was down after PNS intervention,and the PRKACA in the control group decreased after treatment.The trend of PLIN3 in the two groups was the same.The PLIN3 in the treatment group was down after the PNS intervention,and the PLIN3 in the control group was also down after the treatment.ConclusionPNS is effective in treating unstable angina pectoris and blood stasis syndrome.PNS can effectively improve the patient’s electrocardiogram,reduce the time and attack times of myocardial ischemia;PNS can obviously improve the physical activity of the patients with unstable angina pectoris and blood stasis syndrome;PNS can effectively improve the integral of blood stasis syndrome in the patients with blood stasis syndrome of unstable angina pectoris;PNS has the effect of anti inflammation,which may be effective.It is related to the reduction of leukocytes in the blood.Xuesaitong Soft capsule is effective and safe in the treatment of unstable angina pectoris of coronary heart disease.The consistency of let-7b and ADRB2 shows that ADRB2 is very likely to be the target gene for let-7b.In the course of target gene prediction,ADRB2 also belongs to the target gene of let-7b,which has not been verified.The results of this experiment further provide the basis.This study found that PNS up-regulated let-7b and ADRB2,thus regulating downstream signal pathway GS/AC/cAMP/PRKACA/PLIN3,which may be one of the important ways for PNS to achieve therapeutic effect:PNS up regulation of ADRB2/Gs/AC signal molecules,which may be used to reduce the level of adrenalin and norepinephrine in patients with acute myocardial infarction,and thus to improve the level of adrenalin and norepinephrine.Good cardiac contractile and contractile function;PNS downregulation cAMP level to reduce PRKACA,which may reduce myocardial oxygen consumption,reduce cardiac load and inhibit cardiac remodeling;PNS reduces PRKACA level to reduce PLIN3,and its function may be to regulate adipocyte function and reduce blood lipid level. |