Preliminary Study On The Regulatory Mechanism Of CO₂ Fractional Laser Combined With 5-Fluorouracil Ethosomal Gel In The Intervention Of Rabbit Ear Hypertrophic Scar

Objective This study was designed to observe the histological and related cytokines changes in the rabbit ear hypertrophic scars after intervened by CO2 fractional laser(referred to as laser)combined with 5-Fluorouracil(5-FU)ethosomal gel(EG)and explore the regulatory mechanism of intervening rabbit ear hypertrophic scar preliminarily,so as to provide new ideas for the treatment of hypertrophic scar.Methods Hypertrophic scar model was established by the method of making round defect on the ventral surface of New Zealand white rabbit ears,and was given different interventions after molded.The scars were divided into 4 groups: control group,EG treatment group,laser treatment group and combined treatment group(laser plus EG).The scars were observed grossly after 3?7?10?14 days respectively,then the rabbits were executed and specimens from each group of the scar samples were pathologically sectioned and stained with hematoxylin and eosin(HE)to detect the relative thickness and collagen fiber arrangement state.At the same time,RNA was extracted from the samples and got reverse transcription.The expression patterns of collagen type???,Transforming growth factor-?1(TGF-?1),Vascular endothelial growth factor(VEGF)and Interleukin-6(IL-6)which have the most close relationship with scar were detected by real-time quantitative PCR.Results 1.After 4 weeks,the rabbit ear hypertrophic scar tissue was significantly higher than the skin surface,with red color and hard texture(like the ear cartilage),indicating that the models were built successfully.2.Intervention effect: through the observation on different time points,we found that on the 14 th day,the intervention groups had significant difference with control group: color faded,thinner and soft texture;Imagel J software was used to measure the relative thickness of scars after HE stained.The results showed that: combined treatment group <laser treatment group < EG treatment group <control group,and there was a significant statistical difference between the intervention groups and control group.3.The expression pattern of molecules which are most closely related with scar proliferation: after 14 days the m RNA expression levels of collagen type?,? collagen and TGF-?1 was significantly reduced in the intervention groups;the expression level of VEGF decreased like this: combined treatment group< laser treatment group < EG treatment group <control group,and there was a significant difference(p <0.05)between the combined treatment group and control group;the expression of IL-6 increased only in the laser treatment group,and had a significant difference(p <0.05)comparing with the control group;and the combined treatment group and EG treatment group showed no significant change.Conclusions The effect of combined treatment was better than single EG treatment,and was similar to that of single CO2 fractional laser.Preliminary analysis showed the mechanism may be related to the inhibition of collagen type ???,TGF-?1 and VEGF,and the regulation mechanism of IL-6 remains to be further studied.