聚焦超声治疗对外阴低级别鳞状上皮内病变模型大鼠外阴皮肤缺氧诱导因子1α、血管内皮生长因子及突变型p53表达的影响

Impact of focused ultrasound on expression of hypoxia inducible factor-1α, vascular endothelial growth factor and mutant type p53 in vulvar skin of rat models with low grade squamous intraepithelial lesion

目的探讨聚焦超声治疗对外阴低级别鳞状上皮内病变(LSIL)模型大鼠外阴皮肤中缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)及突变型p53(mtp53)表达的影响。方法建立28只外阴LSIL大鼠模型,随机分为治疗组(n=14)及对照组(n=14)。治疗组予以聚焦超声辐照,对照组予超声假辐照(治疗仪无功率输出)。4周后取模型大鼠外阴皮肤行组织病理学观察,并以免疫组织化学方法检测HIF-1α、VEGF及mtp53表达。结果聚焦超声辐照/假照后4周治疗组92.86%(13/14)外阴皮肤基本恢复正常生理结构,对照组71.43%(10/14)进展为高级别鳞状上皮内病变(HSIL)。治疗组大鼠外阴皮肤中HIF-1α、VEGF及mtp53表达均明显低于对照组(P均<0.05)。结论聚焦超声可通过降低HIF-1α、VEGF及mtp53表达,改善局部组织微环境而安全、有效治疗大鼠外阴LSIL。

Objective To explore the impact of focused ultrasound on expression of hypoxia inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF) and mutant type p53(mtp53) in vulvar skin of rat models with low grade squamous intraepithelial lesion(LSIL). Methods A total of 28 rat models with LSIL were established and randomly divided into treatment group and control group(each n=14). The rat models in treatment group were treated with focused ultrasound, while in control group only received sham irradiation(no power output from ultrasonic therapeutic instrument). Histological changes of vulvar skin in SD rats were observed 4 weeks later. The expression of HIF-1α, VEGF and mtp53 protein were detected using immunohistochemistry. Results After 4 weeks of focused ultrasound irradiation/sham irradiation, there were 92.86%(13/14) rats return to normal in treatment group and 71.43%(10/14) rats progressed into high grade squamous intraepithelial lesion(HSIL) in control group. Compared with control group, HIF-1α, VEGF and mtp53 protein levels significantly decreased in treatment group(all P<0.05). Conclusion Focused ultrasound treatment can improve the microenvironment of local vulvar tissue by decreasing the expression of HIF-1α, VEGF and mtp53 in vulvar skin, therefore can be used to treat LSIL safely and effectively in rat models.