Therapeutic Effects Of Focused Ultrasound On Expression Of Notch1,c-fos And TGF-?3 In Vulvar Skin Of Rats With Vulvar Lichen Simplex Chronicus

Vulvar lichen simplex chronicus?LSC?is a vulvar hypopigmentation disease,its etiology and morbidity are still unclear,mainly secondary to various genital itching diseases.The pathological features of LSC are squamous epithelial hyperplasia of the vulvar skin with hyperkeratosis or keratinization,and superficial collagen fibrosis of the dermis.At present,commonly used clinical treatment methods include drug therapy and physical therapy.Conventional drug treatments,such as topical application of steroids,have a long treatment process and are prone to repeated attacks and patients are poorly tolerated.Physical therapy such as:CO2 laser therapy,cryotherapy and bomu light therapy,etc.,although effective to a certain extent,the recurrence rate is higher.Focused ultrasound therapy is a physical therapy that has been widely used in the treatment of vulvar hypopigmentation diseases in recent years.Compared with medical treatment and other physical therapy methods,the advantages of focused ultrasound treatment of vulvar hypopigmentation diseases include good effectiveness,safety and low recurrence rates,which satisfied the patients.Focused ultrasound is effective in the treatment of vulvar lichen simplex chronicus,but the mechanism of its treatment for vulvar disease is rarely studied.Therefore,the molecular mechanism of focused ultrasound in the treatment of vulvar lichen simplex chronicus is studied from pathological examination,electron microstructure examination,protein detection and mRNA detection.Objectives1.SD rats models of lichen simplex chronicus were established.2.To explore therapeutic effects of focused ultrasound on vulvar lichen simplex chronicus of rats and effect of focused ultrasound on expression of notch1,c-fos and transforming growth factor-?3?TGF-?3?in vulvar skin of rat models with vulvar lichen simplex chronicus?LSC?.MethodsThe recent study was divided by:Firstly,establishment of a rat model of vulvar lichen simplex chronicus induced by 7,12-dim-ethylbenzanthracene.Secondly,to investigate the therapeutic effect of focused ultrasound on the expression of notch1,c-fos and TGF-?3 in vulvar skin of SD rats with LSC.1.All SD rats?female,SPF grade,80?used in this experiment were provided by the Animal Experimental Center of Chongqing Medical University.They were divided into two groups including the blank control group?n=10?that did not give any experiment treatment during the whole experiment;the model group?n=70?that was given mechanical stimulation of vulvar skin and applied 0.5%dimethyl benzoanthracene?DMBA?in acetone.The experimental treatment exists12 weeks,and the corresponding experimental treatment of each group is carried out at a fixed time on Monday,Wednesday,and Friday;the entire experimental observation period is 20 weeks.Visually observe the dynamic changes of the vulvar skin.Biopsies were performed on the vulvar skin tissues of rats at 8,12,16,and 20 weeks.After staining,the pathological changes of the vulvar skin tissues were observed under microscope.2.SD rats models with LSC?n=56?were divided into the therapy group?n=28?and the control group?n=28?randomly.The therapy group was treated by focused ultrasound and the control group was treated by shamed focused ultrasound?the instrument had no power output during the treatment course?.At the 4^th week after focused ultrasound treatment,using HE staining observes the pathological changes of vulvar skin in SD rats and using immunohistoche-mistry and western blotting detects the expression of notch1,c-fos and TGF-?3 protein.Results1.In the blank control group,pathological changes were no significant difference during the period.In the model group,56 rats?80%?occurred vulvar lichen simplex chronicus?LSC?at 12 weeks.2.After 4 weeks of focused ultrasound treatment,in therapy group,75.0%?21/28?rats return to normal,17.8%?5/28?rats progressed into LSIL and in therapy group and 7.2%?2/28?rats still exited LSC.In control group,67.9%?19/28?rats progressed into LSIL,21.4%?6/28?rat still exited LSC,and only 10.7%?3/28?rats return to normal?P<0.05?.Total collagen fiber density in the layer of dermis in therapy group was significantly lower than that in control group?P<0.05?,while there were small different between blank control group and therapy group?P>0.05?.Notch1 and c-fos protein levels were significantly decreased and TGF-?3 protein level were significantly increased in control group?P<0.05?,while there were small different between the blank control group and the therapy group?P>0.05?.Conclusions1.SD rats models with vulvar lichen simplex chronicus can induced by DMBA dissolved in acetone solution with mechanical irritation.2.Focused ultrasound treatment vulvar LSC is effective and have low recurrence rate.It may be related to inhibiting superficial collagen fibrosis in the dermis by affecting expression of notch1,c-fos,and TGF-?3 in vulvar skin tissue.