| Objective:To evaluate the effect of drug intervention on the level of inflammatory factors and anxiety in patients with coronary heart disease systematically,the data of randomized controlled clinical study were collected,summarized.The methodological information,bias,characteristics of research objects,and the results of inflammatory factors and anxiety-related scale were analyzed.To explore the mechanism of chaihujialonggumuli decoction inhibiting CXC chemokine-mediated inflammation in rats with anxiety after myocardial infarction.Methods:Study 1:According to the main search terms,the Chinese knowledge resource database(CNKI),Vip Database,WanFang database and PubMed,Cochrane Library,Ovid,Embase,Web of Science were searched.The year of retrieval was from 2010 to now.Literature search and screening were conducted independently by 2 researchers according to inclusion criteria.The quality of literature was evaluated independently by two researchers according to the Risk of bias(ROB bias)scale provided by Cochrane's Handbook,and the quality of outcome evidence was rated by GRADEpro software.Cochrane Revman 5.3 software was used for data analysis.The efficacy was determined by the forest map,and the publication bias was determined by the funnel.If the heterogeneity test suggests that the heterogeneity is large,sub-group analysis or sensitivity analysis was used to explore possible heterogeneity sources.For those studies with large clinical heterogeneity that can not be combined,only descriptive analysis was performed,and the results were represented by forest maps.Study 2:The model of anxiety was established by 21-day unpredictable empty bottle stimulation,the model of myocardial infarction was established by ligating the left anterior descending branch of coronary artery,the cardiac function was evaluated by electrocardiograph and echocardiography,the anxiety like behaviors of rats was evaluated by the elevated maze and open field test.And the cell morphology was observed by HE,Masson,Nissl staining and transmission electron microscope,and the pathway target proteins and genes were detected by immunohistochemistry,Western-Blot,QPCR and ELISA.Results:Study 1:21 articles were included in the study,with the sample size of 2342 cases,1175 cases in the experimental group and 1167 cases in the control group.The mean expression of hs-CRP in intervention group was lower than that in control group[SMD=-1.61,95%CI(-2.14,-1.00),P<0.01];The mean expression of IL-6 in intervention group was lower than that in control group[SMD=-43.31,95%CI(-45.55,-41.07),P<0.01];The mean expression of IL-8 in intervention group was lower than that in control group[SMD=-5.03,95%CI(-8.37,-1.70),P=0.003];The mean expression of IL-17 in intervention group was lower than that in control group[SMD=-33.27,95%CI(-40.15,-26.39),P<0.01];And the mean value of TNF-? expression was lower than that of control group[SMD=-1.18,95%CI(-1.98,-0.38),P=0.004];The Hamilton scale score of anxiety state in intervention group was lower than that in the control group[SMD=-1.97,95%CI(-2.48,-1.46),P<0.01].Study 2:In experiment 1:(1)The content of CXCL12 in bone marrow of rats with myocardial infarction was decreased under chronic stress stimulation:the expression of CXCL12 in bone marrow of rats in compound model group was significantly lower than that in sham operation and myocardial infarction groups(P<0.05);(2)The IOD value of CXCR4 in the myocardial tissue of the complex model group was higher than that in the sham operation group and the myocardial infarction group(P<0.05);(3)After myocardial infarction,the imbalance of CXCL12/CXCR4 biological axis aggravated the inflammatory reaction:the expression of neutrophil elastase in the composite model group was significantly higher than that in the sham operation and myocardial infarction groups(P<0.05),the arrangement of myocardial fibers was disordered,the cytoskeleton structure disappeared,and a large area of necrosis occurred,and a large number of neutrophils and other inflammatory factors infiltrated in the composite model group and myocardial infarction group.In experiment 2:(1)Chaihujialonggumuli Decoction(BFG)inhibited CXCR4/NF-?Expression of inflammatory protein:the expression of CXCR4 protein in BFG group and inhibitor group was significantly lower than that in compound model group(P<0.05),The expressions of NF-?B?IL-1??IL-18 and GSDMD protein were lower than those in the compound model group(P<0.05);(2)The BFG inhibited CXCR4/NF-? Expression of inflammatory protein gene:CXCR4,NLRP3 and NF-?B in the compound model group.Gsdmd protein gene expression was significantly higher than that in sham operation group(P<0.05).Chinese medicine group could significantly inhibit CXCR4,NLRP3 and NF-?B in rats with myocardial infarction and anxiety.GSDMD protein gene expression(P<0.05);(3)The BFG inhibited the expression of related inflammatory proteins in myocardial infarction border area:compared with the sham operation group,the positive rates of NLRP3 and GSDMD immunohistochemical staining in the compound model group were higher(P<0.05),but the expression levels of NLRP3 and GSDMD in BFG group were lower than those in the compound model group(P<0.05);(4)The BFG improved heart function after myocardial infarction:compared with sham operation group,LVEF%and LVFS%of myocardial infarction group and compound model group were significantly decreased(P<0.05),LVEF%and LVFS%of inhibitor group and BFG group were significantly increased(P<0.05),LVIDs and LVIDd%of complex model group and myocardial infarction group were significantly increased(P<0.05)LVIDd was significantly higher than that in sham operation group(P<0.05),LVIDd and LVIDs in inhibitor group and BFG group were significantly lower than those in complex model group(P<0.05);(5)BFG reduced IL-1 ? in peripheral blood compared with the compound model group and myocardial infarction group,the levels of IL-18 and IL-1 ? in peripheral blood were decreased after treatment with BFG(P<0.05);(6)BFG alleviated the anxiety like behavior of rats and regulated the expression of 5-HT and DA protein:the times and residence time of rats in the complex model group were significantly less than those in the sham operation group and myocardial infarction group(P<0.05).Compared with the complex model group,the times and residence time of rats in the complex model group were increased(P<0.05),The protein levels of 5-HT and DA in the hippocampus of the compound model group were significantly lower than those of the sham operation group(P<0.05),and the protein levels of 5-HT and DA in the hippocampus of the BFG and inhibitor group were significantly higher than those of the complex model group(P<0.05).In experiment 3,(1)The BFG inhibited the expression of main inflammatory proteins in hippocampus:NLRP3,GSDMD and IL-1? in hippocampus of rats in compound model group,myocardial infarction group and traditional Chinese medicine group?Compared with the complex model group,BFG treatment group significantly reduced NLRP3,GSDMD and IL-1?,IL-18 in the brain of rats with myocardial infarction(P<0.05);(2)The BFG improved the nerve injury in hippocampus:compared with the compound model group and myocardial infarction group,the Nissl positive area in hippocampus in BFG group increased(P<0.05);(3)The BFG improved the anxiety-like behavior of rats with anxiety following myocardial infarction:compared with the sham operation group,OT%and OE%of rats in the complex model group were significantly decreased(P<0.05),the horizontal and vertical movement scores of rats in the complex model group were significantly decreased(P<0.05),and the activity exploration ability was decreased,Compared with the complex model group,the scores of horizontal movement and vertical movement in BFG group were increased(P<0.05),and the ability of activity and exploration were improved.Conclusions:Study 1:Traditional Chinese medicine has high clinical safety,little side effect and curative effect.It can effectively reduce the expression of inflammatory factors in patients with coronary heart disease and relieve their anxiety.And the method of promoting blood circulation and removing blood stasis has more advantages in decreasing Hs-CRP inflammatory factors in patients with coronary heart disease complicated with anxiety.The expression of CXCL12/CXCR4 bio-axis in the bone marrow and the marginal zone of myocardial infarction was unbalanced,the inflammatory reaction was overactive,and more inflammatory factors were infiltrating the myocardial tissue.CXCR4/NF-?B/GSDMD inflammatory signal pathway is activated by overexpression of CXCR4,chaihujialonggumuli decoction may inhibit the activation of CXCR4/NF-?B/GSDMD inflammatory signal pathway and reduce inflammatory factor infiltration in myocardium by decreasing the expression of CXCR4,it can promote the repair of myocardial cells in the margin area of myocardial infarction and improve the cardiac function,Chaihujialonggumuli decoction can decrease the expression of NLRP3,Caspase-1,GSDMD,IL-1? and I1-18 in the brain after myocardial infarction,regulate the synthesis of neurotransmitter and alleviate anxiety-like behavior. |
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