| Objective: To systematically evaluate the clinical efficacy of salvia miltiorrhiza in the treatment of hypertrophic scars,explore the possible mechanism of salvia miltiorrhiza in the treatment of hypertrophic scars,and provide a reference for clinical scar drug treatment.Methods:1.Computer retrieval of English and Chinese databases(including clinical controlled trial databases Cochrane Library,Embase,Pub Med,Vip Chinese journal database,China Knowledge Network,and Wanfang Data Knowledge Service Platform)was conducted from the establishment of the database to September 2020.At the same time,conference materials,degree papers,and references to be included in the literature were searched.The key words are Salvia miltiorrhiza,Red Ginseng,Blood Ginseng,Red Ginseng,Cryptotanshinone,Cicatrix,Cicatrices,Scar,Salvia miltiorrhiza,Cryptotanshinone,Tanshinone,TanshinoneⅡA,Sodium tanshinol,Compound Danshen Dripping Pills,Cicatrix,Cicatrices,Scar.Screening all clinical randomized controlled studies of salvia miltiorrhiza in the treatment of hypertrophic scars,regardless of whether the blind method or allocation concealment is used,and regardless of the patient’s nationality,race,or age.The included literature was analyzed using software(Rev Man 5.4),in which the standard mean difference or weighted mean difference was used for numerical variables;for binary variables,the 95% confidence interval(95% CI)was calculated for all combined statistical analysis data using odds ratios,with P<0.05 indicating statistical significance.2.Screening the active ingredients and drug targets of Salvia miltiorrhiza through the TCMSP database,obtaining the disease targets of hypertrophic scars in the Gene Cards database,performing Wayne diagram analysis on the drug targets and disease targets,and taking the intersection as the action target of Salvia miltiorrhiza for treating hypertrophic scars.Construct a drug component target disease network diagram using Cytoscape software.Build a protein interaction network through String website,screen its key protein modules and Hub genes using Cytoscape software,and conduct GO function annotation and KEGG pathway enrichment analysis in DAVID database.3.A total of 114 hypertrophic scar models were constructed in 12 healthy male Japanese white rabbits and randomly divided into three groups,namely,the control group,the tanshinone group,and the triamcinolone acetonide group.Starting from 28 days after modeling,the control group was injected with physiological saline,the tanshinone group was injected with tanshinone ⅡA sodium sulfonate injection,and the triamcinolone acetonide group was injected with triamcinolone acetonide injection once every 7 days,for a total of 4injections.Scar scale scores,Masson staining,and Sirius red staining were performed 28 and56 days after modeling,respectively.Samples were taken 56 days after molding to detect relevant indicators.Real-time fluorescence quantitative detection of hypoxia inducible factor-1α(HIF-1α)、 Transforming growth factor β1(TGF-β1)Relative expression of vascular endothelial growth factor(VEGF)gene,Western method for detecting HIF-1α,TGF-β1 and VEGF protein expression level.Results:1.Finally,6 relevant articles meeting the standards were included,with a total of 778 patients.The combined result of significant therapeutic efficacy was OR=3.83,with a 95% CI of 2.65-5.54.The results showed that there was a significant statistical difference between the salvia miltiorrhiza treatment group and the control group,that is,the significant therapeutic efficacy rate of the salvia miltiorrhiza treatment group was significantly higher than the control group.The combined result of the total effective rate of treatment was: OR=6.94,with a 95% CI of 2.53 to 19.06.The results showed that there was a statistically significant difference between the salvia miltiorrhiza treatment group and the control group,that is,the total effective rate of treatment in the salvia miltiorrhiza treatment group was significantly higher than the control group.After 3 months of treatment,the combined result of scar score was: MD=-0.96,with a 95% CI of-2.29 to 0.36.The results showed that there was no significant difference between the salvia miltiorrhiza treatment group and the control group,that is,the scar score of the salvia miltiorrhiza treatment group after 3 months of treatment was not significantly improved compared to the control group.After 6 months of treatment,the combined result of scar score was: MD=-1.37,with a 95% CI of-2.44 to-0.30.The results showed that there was a statistically significant difference between the salvia miltiorrhiza treatment group and the control group,that is,the scar score of the salvia miltiorrhiza treatment group after 6 months of treatment was significantly improved compared to the control group.2.59 active ingredients,138 drug targets,4571 disease targets,and 90 therapeutic targets of Salvia miltiorrhiza for hypertrophic scars were selected.The drug component target disease network shows that luteolin,tanshinone Ⅱ A,and other major components of Salvia miltiorrhiza in the treatment of hypertrophic scars,and it involve signal pathways such as HIF-1,TNF,PI3K-AKT.3.At 28 days after surgery,there was no statistically significant difference in scar scale scores among the groups.Compared with the control group on the 56th day after surgery,the scores on the scar scale in the tanshinone group and triamcinolone acetonide group decreased significantly(P<0.05).On the 28th day of modeling,Masson staining sections of scars in each group showed blue staining of collagen fibers under an upright fluorescent microscope,and the upper dermis was filled with a large number of dense collagen bundles,arranged in a curly and irregular shape,consistent with the appearance of hypertrophic scars;At day 56,the accumulation of collagen fibers in each group was decreased compared to that at day 28,and the arrangement was more regular.Compared with the control group,the collagen bundles in the dermis of the tanshinone group and triamcinolone acetonide group became thinner,with small blood vessels between the collagen bundles,and some collagen fibers arranged in a basket like manner similar to the normal collagen arrangement in the dermis.At 28 days,Sirius red staining showed that the dermis of each group of scars was filled with a large number of structurally disordered collagen tissue,in which the content of type Ⅰ collagen fibers was significantly higher than that of type Ⅲ collagen fibers,consistent with the characteristics of hypertrophic scars;At 56 days,the content of greenish type Ⅲ collagen fibers scattered around red and yellow type I collagen fibers in the dermis of each group increased,but compared with the control group,the increase trend was more obvious in the tanshinone group and triamcinolone acetonide group,and the arrangement of red and yellow type I collagen fibers was more regular.Compared with the control group,the expression of HIF-1α,TGF-β1,and VEGF genes in the tanshinone group and triamcinolone acetonide group decreased significantly(P<0.05).Compared with the triamcinolone acetonide group,the expression of HIF-1α,TGF-β1,and VEGF in the tanshinone group decreased significantly(P<0.05).Compared with the control group,the expression of HIF-1α,VEGF,and TGF-β1proteins in the tanshinone group and triamcinolone acetonide group decreased significantly(P<0.05).Compared with the triamcinolone acetonide group,the expression of HIF-1α and VEGF protein in the tanshinone group decreased significantly(P<0.05).Conclusion:1.Salvia miltiorrhiza treatment can significantly improve the treatment efficacy and total effective rate of clinical scar patients,and has a good clinical therapeutic effect on scar patients.2.Salvia miltiorrhiza can improve the hypoxic state,inflammatory response,and balance between fibroblast proliferation and apoptosis in PS by regulating signal pathways such as HIF-1,TNF,MAPK,PI3K-Akt,and Jak-STAT.It has the characteristics of multicenter,multi target,and multiple pathways.3.Tanshinone ⅡA can inhibit the formation of rational scars in rabbit ears and inhibit HIF-1α signal activation. |
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