| Background and Objective:The incidence of aortic aneurysm(Aortic Aneurysm,AA)is increasing year by year,but its mechanism is not completely clear.Based on the biological similarity between animals and human beings,people can study its potential mechanism through animal experiments.It has been known that matrix metalloproteinases(Matrix Metalloproteinase,MMPs)are a kind of endopeptidases with stable dependence on metal ions(such as calcium and zinc)and the ability to degrade extracellular matrix,which play an important role in tissue repair and production.The increase of its activity level may be involved in the occurrence and development of aneurysms.In this study,we retrospectively analyzed the data of various experimental aneurysm models,compared the relationship between the incidence and expansion of aneurysms and the changes of MMPs activity,and used the methods of systematic review and meta-analysis of animal experiments to evaluate the role and significance of MMPs in the occurrence and development of aneurysms.Methods and materials:The databases of Pub Med,Web of Science,Embase,China Biology Medicine disc(CBM),China How Net(CNKI),Chongqing weipu database(VIP)and Wan Fang Data were searched for animal control experiments published in Chinese and English related to MMPs and AA,which must include qualitative and/or quantitative detection of MMPs activity.The main therapeutic indicators are aneurysm formation and aneurysm diameter change.The search time began from the establishment of the database to February 28,2021.Inclusion criteria:the subjects were animals,and their species,sex,age,intervention measures and intervention time were unlimited;the type of study was control experimental study,which required to set up a blank control group to eliminate the effects of normal growth;MMPs directly detected increased or decreased and had statistical effects;the main outcome indicators:1.The occurrence of AA;2.Dilation of aortic diameter.Exclusion criteria:Only the control group and no blank control group were set up to exclude the experimental results caused by normal growth;Experimental studies with serious lack of information and unreliable data;Experimental studies with different baseline levels between the two groups;No data that can be used for literature analysis,or incorrect data analysis methods;Repetition of literature;Review of literature.According to the inclusion and exclusion criteria,two researchers screened the literature,extracted data and evaluated the quality of the studies which were considered relevant for this analysis with CAMARADES(revised)list.Rev Man 5.4 software was used for statistical analysis.Meta-analysis of indicators that can be combined and analyzed;For many research results with good homogeneity,the fixed effect model is used to combine and analyze them;The indicators with obvious statistical heterogeneity(heterogeneity test P<0.10,I~2≥50%)were analyzed by random effect model,and subgroup sum or sensitivity analysis was carried out to explore the possible sources of heterogeneity;If the analysis cannot be combined,the hierarchical analysis is adopted,and the research that cannot be layered is described by the overall analysis method.In order to explore the influence of different MMPs activity expression on AA,the change level of MMPs activity was analyzed according to"high expression"and"inhibition expression",and the curative effect indexes of"high expression group"and normal group and"inhibition expression"and intervention group were compared.Evaluation of publication bias by funnel chart.Results:A total of 4259 articles were obtained for this analysis.According to the inclusion criteria of this study,a total of 26 literatures were included.According to the CAMARADES(revised)list,the quality scores of 13articles were 7,11 articles were 6,2 articles were 5,and the median quality score was 6.5.Our results showed that compared with the normal group,high expression of matrix metalloproteinase could promote the formation of aortic aneurysm in animals[Relative risk degree(OR)=43.3,95%Confidence Intervals(CI)=(19.11,98.30),P<0.00001],and dilate the diameter of aorta in mice[Standardized Mean Difference(SMD)=10.67,95%CI=(3.95,17.39),P=0.002],rat[SMD=11.27,95%CI=(6.88,15.65),P<0.00001]and rabbits[SMD=16.98,95%CI=(0.51,33.46),P=0.04].Compared with the model group,reducing the expression of MMPs could inhibit aortic aneurysms[OR=0.15,95%CI=(0.09,0.24),P<0.00001]and reduce the diameter of expansion of aortic aneurysms in mice[SMD=-5.59,95%CI=(-7.51,-3.66),P<0.00001],rats[SMD=-3.53,95%CI=(-4.70,-2.37),P=<0.00001],and rabbits[SMD=-7.05,95%CI=(-10.60,-3.49),P=0.0001].Conclusion:In different experimental AA models,the increase of MMPs activity was proportional to the incidence of AA and the degree of aortic diameter dilatation,suggesting that the increase of MMPs activity may be related to the pathophysiological process of the occurrence and development of AA.The change of MMPs activity may become an important target for prevention and treatment of AA in the future. |
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