透明质酸酶联合尿激酶静脉持续注射治疗透明质酸动脉栓塞的效果观察

Continuous intravenous injection of hyaluronidase combined with urokinase in the treatment of hyaluronic acid arterial embolism

目的探讨静脉内持续注射透明质酸酶(HAase)联合尿激酶是否对透明质酸(HA)动脉栓塞皮瓣缺血有治疗效果。方法(1)构建腹壁浅动脉HA栓塞动物模型:采用SD大鼠24只,以腹壁浅动脉为供血动脉在腹白线左右两侧各制作一正方形岛状皮瓣(面积为2 cm×2 cm,蒂宽为2 mm)。将每只大鼠左、右两侧皮瓣分别作为实验皮瓣和自身对照皮瓣,实验皮瓣在完成皮瓣制作后,于腹壁浅动脉内注射HA 10μl,自身对照皮瓣只完成皮瓣制作、剥离血管,不做栓塞处理。(2)实验分组及HA栓塞模型的治疗:将大鼠采用完全随机法(抽签法)分为A、B、C、D 4组,每组6只,在栓塞动物模型建立成功45 min后,分别经尾侧静脉以微量注射泵持续注射HAase(2000 IU/kg)+尿激酶(50000 IU/kg)、HAase(2000 IU/kg)、尿激酶(50000 IU/kg)、生理盐水,每组所注射溶液体积为6 ml,12 min注射完毕。观察大鼠全身状况及术区的皮肤色泽、水肿、淤血、皮肤坏死等情况,分别于栓塞后即刻、3 d、5 d、7 d拍照对比。用Photoshop软件进行图像分析,采用像素法测量术后7 d皮瓣的存活面积百分比。存活面积百分比多组间比较采用单因素方差分析,组间两两比较采用LSD-t检验。结果术后即刻4组皮瓣均呈苍白色,无明显肿胀,术后3 d内,均出现不同程度肿胀,术后3~5 d内肿胀基本消退,由不同程度暗红色淤斑逐渐转变至暗紫或黑色,术后7 d坏死区域皮瓣逐渐变硬,分界明显。4组皮瓣呈不同程度坏死。皮瓣的术后反应中A组最轻,B、C两组表现相似,均在A组、D组之间,D组术后反应最重。至术后7 d,A、B、C、D组皮瓣成活面积百分比分别为90.30%±5.95%、52.63%±6.90%、51.14%±5.95%、7.70%±2.18%。A组的皮瓣成活面积百分比高于B、C、D组中任意一组,差异均有统计学意义(方差分析:P<0.01;LSD-t检验:P值均<0.01)。结论HAase联合尿激酶静脉持续注射可有效改善因HA动脉栓塞导致的皮瓣缺血,增加组织灌注,增加皮瓣成活面积。

Objective To investigate the efficacy of continuous intravenous injection of hyaluronidase(HAase)combined with urokinase(UK)in the treatment of ischemia of hyaluronic acid(HA)arterial embolized skin flap.Methods(1)Establish an animal model of superficial abdominal artery embolization with HA:24 SD rats were used to make a square island flap(2 cm×2 cm,the width of the pedicle is 2 mm)on the left and right sides of the abdominal white line with superficial epigastric artery as feeding artery.The left and right flaps of rats were used as experimental group and control group.After the preparation of the experimental skin flap,HA 10μl was injected into the superficial abdominal artery,while the self-control flap was only made and the vessels were peeled off without embolization.(2)The rats were randomly divided into A,B,C and D groups by drawing lots with 6 rats in each group,After the successful establishment of embolic animal model of 45 min,HAase(2000 IU/kg)+UK(50000 IU/kg),HAase(2000 IU/kg),UK(50000 IU/kg)and normal saline were continuously infused through caudal vein with microinjection pump.The volume of solution in each group was 6 ml in 12 minutes.The general condition of rats and the skin color,edema,congestion and skin necrosis in the operation area of rats were observed,which were photographed and compared immediately,and at 3 days,5 days and 7 days after embolization.The images were analyzed by Photoshop software,and the percentage of survival area of the flap after operation 7 days,was measured by pixel method.The percentage of survival area was compared by single factor analysis of variance(ANOVA)and head-to-head comparison by LSD-t test.Results Immediately after operation,all the flaps in the four groups were pale and there was no obvious swelling.All the flaps showed different degrees of swelling within 3 days after operation,and the swelling basically disappeared within 3-5 days after operation,and gradually changed from dark red ecchymosis to dark purple or black.Seven days after operation,the necrotic area flap gradually hardened and its boundary was obvious.The skin flaps of the 4 groups showed different degrees of necrosis.The postoperative reaction of the flap was the slightest in group A,the performance of group B and C was similar,which were both between group A and group D,and there was the heaviest postoperative reaction in group D.At 7 days after operation,the percentage of survival area of flaps in groups A,B,C and D was 90.30%±5.95%,52.63%±6.90%,51.14%±5.95% and 7.70%±2.18%,respectively.The percentage of survival area of skin flap in group A was significantly higher than that in groups B,C and D(analysis of ANOVA:P<0.01;LSD-t test:P<0.01).Conclusions Continuous intravenous infusion of HAase combined with UK can effectively alleviate the flap ischemia caused by HA artery embolism,increase tissue perfusion and increase the survival area of the flap.