Radiofrequency Ablation Therapy For Pathological Scar And The Study Of Drug Screening Assays Based On Gene Expression Profile

Objectives:To evaluated the clinical efficacy of the radiofrequency ablation forpathological scar. Screening differentially expressed genes of the pathological scartissue was done using the gene expression profile chip. The drug was selectedbased on the data of genes with the bioinformatics methods. The efficacy of theselected drug was validated in the animal model of rabbit ear.Methods:1) The pathological scar tissue was ablated by the type II radiofrequency ablationinstrument and the efficacy of this treatment was assessed with the Vancouver scarscale.2) Screening differentially expressed genes between the pathological scar tissueand the normal skin tissue was done. Analysis of the Go and Pathway for thesedifferentially expressed genes was done to explain the mechanism of scar formation.3)Input the differentially expressed genes in the Cmap Database on line, screening thecompound or drug for pathologic scarring by bioinformatics.4) The paclitaxel wasselected and the Chemical Confecting for it was done with differential concentrations.Inject the compounding of the paclitaxel in the hypertrophic scars of rabbit ears. Thescars histomorphology under electron microscope was observed to evaluate the effectof the paclitaxel on the hypertrophic scars tissue of rabbit ears and find the bestmedication range of the drug concentrations.Results:1) After be treated with radiofrequency ablation treatment of pathologic scar, thescar's color, thickness, softness have been significantly improved. After be treated byradiofrequency ablation, the color, thickness and softness of scar had beensignificantly improved.2) There were5001up or down-regulated genes in2-fold DEGs,956up or down-regulated genes in5-fold DEGs, and114up ordown-regulated genes in20-fold DEGs. The related pass way with the up-regulatedgenes was such as: ECM-receptor interaction, Focal adhesion; O-Glycan biosynthesis,Cytokine-cytokine receptor interaction, TGF-beta signaling pathway,Glycosaminoglycan degradation, Toll-like receptor signaling pathway, Cell adhesionmolecules, Tumor-associated signaling pathway, and Regulation of actin cytoskeletonetc. The related pass way with the down-regulated genes was such as: Drugmetabolism-cytochrome P450, Arachidonic acid metabolism, Urea cycle andmetabolism of amino groups, Androgen and estrogen metabolism, Tyrosine orPhenylalanine metabolism, Retinol metabolism, Biosynthesis of steroids, lipidmetabolism, and amino acid degradation etc.4)The molecular function of theup-regulated genes was such as: protein binding, metal ions binding, extracellularmatrix structural constituent, peptidase activity, integrin binding, and transcriptionfactor activity etc. The molecular function of the down-regulated genes was such as:enzyme activity, the binding and movement of ions, and the activity of ion channel etc.5) The related biological process of the up-regulated genes was such as: cell adhesion,collagen fibril organization immune response, proteolysis cell differentiation, cellsignal transduction, cell hypoxia response, cell matrix adhesion integrin-mediatedsignaling pathway, and nerve bone development etc. The related biological process ofthe down-regulated genes was such as: cellular redox reactions, cell metabolism andsynthesis of lipids and inflammatory response etc.6)16drugs which have thenegative enrichment with higher scores were selected from the the Cmap database.7)The fibroblast proliferation, collagen deposition, and angiogenesis of hypertrophicscars of rabbit ears could be inhibited by the paclitaxel. Within certain range ofconcentrations, the degree of scars was negatively correlated with the concentrationsof drug.Conclusion:1)After be treated by RF ablation, the color of pathological scars would be fade,the thickness be flattening, and the contracture be alleviate. Compared with traditionalsurgery, it is an ideal method to dispel scars.2) The pathological scar related to dynamic expression of multiple genes and gene pathways. The multiple genes andpathways interact in network model.3) In anticancer drugs, the cell cycle inhibitorsmay be good curative effect in inhibiting the pathological scar.4) The fibroblastproliferation, collagen deposition, and angiogenesis of hypertrophic scars of rabbitears could be inhibited by the paclitaxel. Paclitaxel would be an idea drug to curepathological scar.