超声破坏微泡对大鼠皮肤创面愈合影响的实验研究

Effect of microbubble destruction with ultrasound on wound healing in rats

目的 探讨超声破坏微泡（声诺维）对大鼠皮肤创面愈合的影响.方法 96只SD大鼠建立皮肤创面模型后随机分成4组：超声破坏微泡组、单纯微泡组、单纯超声组和对照组.超声破坏微泡组经鼠尾静脉注射微泡造影剂0.5 ml,同时用声强度1 MHz、2.0 W/cm^2超声辐照3 min单纯微泡组经鼠尾静脉注射微泡造影剂0.5 ml;单纯超声组经鼠尾静脉注射生理盐水0.5 ml,同样条件超声辐照3 min对照组经鼠尾静脉注射生理盐水0.5 ml.于创伤后第1、3、5、7、14、21 d利用HE染色和免疫组化方法 观察各组创面肉芽组织生长及血管内皮生长因子（VEGF）表达的情况.结果 HE染色：伤后第7 d,超声破坏微泡组肉芽组织明显比其他3组厚,新生毛细血管均垂直于创面生长,其他3组毛细血管排列紊乱.免疫组化观察VEGF表达变化：超声破坏微泡组在第3 d形成表达高峰,其他3组表达高峰在第5～7 d.结论 超声破坏微泡可以提高大鼠背部皮肤的创面愈合质量;新生肉芽组织成熟早,创面愈合加速.超声破坏微泡时产生的高温、高压及某些化学效应可以刺激内源性VEGF分泌,促进血管生成,从而促进创面愈合.

Objective To investigate the effect of microbubble（Sono Vue） destruction with ultrasound on wound healing in rats. Methods Total 96 SD rats were accepted one rounded whole-layer skin incision on back each other and randomly divided into four groups：microbubble destruction with ultrasound（US ＋ MB）,microbubble（MB）, ultrasound（US） and control group. Rats in US ＋ MB group were injected with 0.5 ml microbubble contrast agent via tail vein,and then ultrasound irradiated for 3 minutes immediately. MB group were injected with 0.5 ml microbubble contrast agent. US group were injected with 0.5 ml physiological saline,and then ultrasound irradiated for 3 minutes immediately under the same condition. Control group were injected with 0.5 ml physiological saline. Feed each rat in single cage. On day 1,3,5,7,14 and 21 after wound creation,the excised wound tissues were analyzed by histology and VEGF expression in wounds by immunohistochemistry. Results HE staining： On day 7, wounds of US ＋ MB group displayed the most accumulation of granulation tissue and all new capillaries were perpendicular to the wound surface, but the new capillaries of other 3 groups were disordered. Immunohistochemical examination of VEGF expression：the peak expression appeared on day 3 in US ＋ MB group, other 3 groups were on day 5 to day 7.Conclusions US ＋ MB treatment could improve the quality of wound healing and granulation tissues were maturated earlier than MB, US treatment and control group, which could accelerate wound healing. High temperature,high pressure and some kind of chemistry effecs induced by microbubble destruction with ultrasound can stimulate the secretion of endogenous VEGF, which may be the mechanism of promoting angiogenesis and wound healing.