The Efficacy And Some Mechanisms Of Bupleurum And Longgu Oyster Soup In The Treatment Of Coronary Heart Disease With Anxiety

Cardiovascular disease is a leading cause of mortality and morbidity worldwide.Acute myocardial infarction(AMI)associated fatal conditions,such as heart failure and sudden cardiac death are an enormous psychological and financial burden on patients and society.The inflammatory response caused by injured myocardium initiates ventricular remodeling and myocardial apoptosis,leading to dysfunctional myocardium.Anxiety is a risk factor for cardiovascular disease and is frequently associated with inflammation induced by the injured myocardium.With an incidence rate of 25%in acute coronary syndrome(ACS)patients,anxiety is regarded as a chronic condition that can persist for up to 1 year in half of the post-ACS patients.Enhanced anxiety in 3 months following myocardial infarction predicts adverse cardiac events and mortality.Given its high morbidity and association with poor cardiac health,it is clear that patients suffering from ACS require coordination of mental health care and cardiac treatment,also known as psycho-cardiology therapy.Bone marrow mesenchymal stem cells(BM-MSCs)are non hematopoietic stem cells that exist in bone marrow and have potential of self renewal and multipotential differentiation.BM-MSCs circulation includes mobilization,homing and paracrine,which play a key role in myocardial repair after AMI.However,the spontaneous mobilization of BM-MSCs is not insufficient to achieve desired protective effects.We discussed the psycho-cardiology therapy of traditional Chinese medicine from literature research,clinical research and basic research systematically in this study.We also explored the psycho-cardiology effects of chaihulonggumulitang(BFG),a classical traditional Chinese medicine prescription based on the BM-MSCs circulation.Study1 Chinese herbal medicine therapy for coronary heart disease with anxiety:a systematic review of randomized controlled trialsObjective:To evaluate the effectiveness and safety of CHMs for CHD complicated with anxiety.Methods:Randomized controlled clinical trials(RCTs)with parallel-groups were included after searching through electric-databases from inception to May,2017.Meta-analysis was undertaken with RevMan 5.3 software.Cochrane risk of bias tool was used to assess the methodological quality of RCTs.The overall quality of the evidence was evaluated by GRADE profiler software(version 3.6 for Windows).Self-evaluation for this systematic review was also conducted following the Assessment of Multiple Systematic Reviews(AMSTAR)and Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)checklist reporting guidelines.Results:23 RCTs enrolling 1654 patients were included in this systematic review.The combination therapy(CHMs combined with anxiolytic)appeared to be superior to anxiolytic in terms of reducing the SAS scale score[Mean Difference(MD),-12.25;95%confidence interval(CI),-14.01 to-10.48;P<0.00001;n=220;eliminating method);(MD,-3.92;95%CI,-5.48 to-2.35;P<0.00001;n=270,tranquilizing method),improving the total effect rate[Relative Risk(RR),1.26;95%CI,1.08 to 1.46;p=0.004,n=159,eliminating method]and reducing the TCM symptoms scores(MD,-2.24;95%CI,-4.25 to-0.23,p=0.03,n=61,tranquilizing method)with a lower incidence of adverse events(RR,0.46;95%CI,0.25 to 0.85;p=0.01;n=358:,tonifying method).CHMs demonstrated benefits in lowering the score of HAMA scale(MD,-6.77;95%CI,-8,16 to-5.37,p<0.00001,n=148,tonifying method),lowering the score of SAS scale(MD,-10.1;95%CI,-13.73 to-6.30;p<0.0001;n=148,tonifying method)and reducing the TCM symptoms scores(MD,-2.18;95%CI,-3.12 to-1.24,p<0.00001,n=128,tranquilizing method).Meta-analysis couldn't be conducted in some outcomes owing to the high heterogeneity.Nevertheless,CHMs displayed own superiority.However,the evidence was rated as "low" according to the CRADE criteria due to the low quality of included studies.This study received a "yes" for all the items in the AMSTAR and PRISMA.Conclusions:We got a low evidence that CHMs,which had less side effects,showed potentially benefits to patients of CHD complicated with anxiety.While the results should be interpreted with caution.Trails with higher quality are required to verify the effectiveness and safety of CHMs for CHD complicated with anxiety.Study 2 Chaihulonggumultang shows psycho-cardiology therapeutic effects on patients of coronary heart disease with anxiety.Objective:To evaluate the effectiveness and safety of Chaihulonggumulitang(BFG)for CHD complicated with anxiety.Methods:A randomized double-blind,placebo-controlled parallel design was applied in this study.Sixty cases of patients with coronary heart disease and anxiety were randomly divided into the BFG group and the control group.Patients in the BFG group were treated with BFG,while those in the control group received placebo treatment.After 4 weeks of treatment,the improvement of angina pectoris,HAMA scale score and function of liver and renal were measured.Results:After 4 weeks treatment,the effective rate of angina pectoris in the BFG group was higher than that of control group(P<0.05).The HAMA score of BFG group was lower than that of control group(P<0.05).No functional lesion of liver and kidney was found in both groups.Conclusions:BFG can improve the angina pectoris and anxiety of patients with coronary heart disease and anxiety effectively.Study 3 Chaihulonggumultang shows psycho-cardiology therapeutic effects on acute myocardial infarction by enhancing bone marrow mesenchymal stem cells mobilizationObjective:This study aimed to investigate the psycho-cardiology effects of Chaihulonggumulitang(BFG),a classical traditional Chinese medicine prescription and its potential mechanisms in rats with acute myocardial infarction(AMI)in vitro and in vivo.Methods:This study included in vitro study and in vivo study.Primary BM-MSCs were isolated by the method of whole bone marrow adherence in vitro.BM-MSCs of passage 3 were divided in BFG group,control group and blank group.Cells in the BFG group were treated with complete medium containing 5%BFG medicated serum,while those in the control group were treated with complete medium containing 5%rat serum.Cells cultured with complete medium served as the blank group.Tablet scratch assay and Transwell assay were used to detect the mobilization of BM-MSCs,while ELISA was used to detect the paracrine of BM-MSCs in vitro.Left anterior descending coronary artery ligation was used to establish the rats model of AMI in vivo.Rats were randomly divided into three groups:model group,sham group and BFG group.Rats in each group were further divided into three subgroups according to the duration of administration of BFG(3days,7days and 14days).Function and structure of the left ventricle were assessed by echocardiography.Histopathological change in heart was evaluated by HE staining and Masson staining.The anxiety degree was measured by open-field test(OFT)test and elevated plus-maze test(EPM).Expression of the 67KDa isoform of glutamic acid decarboxylase(GAD76)in the brain hippocampus was detected by inimunohistochemistry.Expression of receptor of glutamate(NMDAR1)and receptor of y-amino butyric acid(GABAAR)in the brain hippocampus were evaluated by real-time quantitative RT-PCR.Level of adrenaline in peripheral blood was detected by Enzyme-linked immunosorbent assay(ELISA).The positive cells of CD90,CD 105,CD54 and CD 106 in peripheral blood and bone marrow were detected by flow cytometry assay.The positive cells of CD 105 in the marginal region of myocardial infarction was measured by imunohistochemistry.Contents of stem cell factor(SCF),TNF-a and NF-?B in peripheral blood and BM-MSCs paracrine factors IGF-1 and FGF-2 in the marginal region of myocardial infarction were detected by ELISA.Expression of NGF and GAP43 in the marginal region of myocardial infarction was detected by WB and real-time quantitative RT-PCR.Results:Results of the in vitro tablet scratch experiment showed that cells treated with BFG serum showed a greater cell migration into a cell-free area than cells in other groups(P<0.05).In addition,more cells treated with BGF serum migrated from the upper chamber to the lower surface of the membrane than cells in the control and the blank group.Contents of IGF-1 and FGF-2 of BFG group in culture supernatant were higher than those in the control group and the blank group(P<0.05).Echocardiography showed that rats of the model group had lower LVEF and LVFS compared with those in the sham group(P<0.05).Meanwhile,higher LViDd,LVEDV,LViDs and LVESV were found in rats of the model group(P<0.05).The LVAWTd and IVSTd of rats in the model group were also significantly decreased(P<0.05).All indexes of echocardiography were obviously improved in rats of the BFG group(P<0.05).Rats in the model group showed a lower horizontal movement in OFT and spent significantly lower time in the open arms in EPM compared with those of the sham group(P<0.05).Level of GAD in hippocampal CA3 region of rats in the model group decreased over time,along with the down regulation of NMDAR1 mRNA and GAB AAR mRNA compared with those in the sham group(P<0.05).Level of adrenaline in peripheral blood also decreased in rats of the model group(P<0.05).All the anxiety related indexes in the BFG group were better than those in the model group(P<0.05).The number of CD90 and CD 105 positive cells in the peripheral blood and bone marrow,the number of CD 105 positive cells in the marginal area of the infarction,the BM-MSCs paracrine factor IGF-1 and FGF-2,and the content of SCF in the peripheral blood in rats of the model group were higher than those in the sham group(P<0.05).Indexes of BM-MSCs circulation in the BFG group were superior to those in the model group(P<0.05).The contents of NF-kB and TNF-a in the peripheral blood,and the expression of NGF and GAP43 protein and mRNA in the marginal area of the infarction in rats of the model group were higher than those in the sham group(P<0.05).The indexes of inflammation and sympathetic remodeling in the BFG group were superior to those in the model group(P<0.05).Conclusions:Enhanced mobilization and paracrine of BM-MSCs by BFG may contribute to the anti-inflammatory effects,thus leading to the improvement of heart damage and anxiety and sympathetic remodeling developed from myocardial infarction.