聚焦超声降低SD大鼠外阴慢性单纯性苔藓复发率的机制

Focused ultrasound therapy for reducing recurrence of vulvar lichen simplex chronicus in rats: efficacy and mechanism

目的通过观察聚焦超声治疗SD大鼠外阴慢性单纯性苔藓(LSC)模型后SD大鼠外阴皮肤组织真皮层胶原纤维化的变化,探寻聚焦超声降低SD大鼠外阴慢性单纯性苔藓模型复发率的机制。方法建立50只雌性大鼠LSC模型,随机分为治疗组和对照组(n=25)。治疗组采用聚焦超声治疗,对照组大鼠采用聚焦超声假辐照治疗。聚焦超声治疗前后,HE染色观察外阴组织学病理变化,masson染色鉴定SD大鼠外阴皮肤组织真皮浅层胶原纤维的密度,电镜下观察真皮浅层胶原纤维超微组织结构。免疫组化和Western blot检测notch1和c-fos在外阴皮肤组织中的表达,比较组间差异。结果经过聚焦超声干预的治疗组大鼠中,16%(4/25)大鼠继续进展为外阴低级别鳞状上皮内病变,4%(1/25)大鼠仍为LSC,80%(20/25)实验大鼠外阴皮肤恢复正常。经聚焦超声假辐照治疗的对照组中有19只(76%)大鼠会继续进展为外阴低级别鳞状上皮内病变,3只(12%)仍然表现为LSC,3只(12%)恢复正常,两组间治愈率差异有统计学意义(P<0.05)。治疗组真皮浅层胶原纤维密度明显低于对照组,且notch1和c-fos在治疗组外阴组织中的表达明显低于对照组(P<0.05)。结论聚焦超声治疗可能通过影响外阴皮肤组织中notch1和c-fos的表达,抑制真皮浅层胶原纤维化,从而降低外阴慢性单纯性苔藓的复发率。

Objective To explore the changes of collagen fibrosis in the vulva skin of SD rats with lichen simplex chronicus(LSC)after focused ultrasound therapy and explore the mechanism by which focused ultrasound reduces the recurrence of vulvar LSC. Methods Fifty female SD rat models of vulvar LSC were established and randomly divided into the treatment group and the control group(n=25) for treatment with focused ultrasound and sham treatment, respectively. Before and after the treatment, vulvar skin tissues were sampled to observe the pathological changes with HE staining and assess the density of collagen fibers using Masson staining. The ultrastructure of the collagen fibers in the superficial dermis was observed using transmission electron microscopy. The expressions of notch1 and c-fos in the vulvar tissue were detected by immunohistochemistry and Western blotting. Results After 4 weeks of focused ultrasound therapy, 16%(4/25) of the rats in the treatment group showed lesion progression to LSIL, 4%(1/25) still had LSC, and 80%(20/25) showed normal vulvar skin. In the control group, progression to LSIL occurred in 19(76%) rats, 3(12%) rats still showed LSC, and only 3(12%) had normal vulvar skin. The difference in the cure rate differed significantly between the two groups(P<0.05). The density of collagen fibers in the superficial dermis and the expressions of notch1 and c-fos in the vulvar skin were significantly lower in the treatment group than in the control group(P<0.05). Conclusion Focused ultrasound therapy can inhibit superficial collagen fibrosis of the dermis by lowering the expressions of notch1 and c-fos in the vulvar skin to reduce the recurrence of vulvar LSC in rats.