硝普钠联合透明质酸酶和尿激酶治疗大鼠腹壁浅动脉透明质酸栓塞的研究

Sodium nitroprusside combined with hyaluronidase and urokinase in treatment of superficial epigastric arterial embolization in Sprague-Dawley rats

目的探讨静脉内硝普钠联合透明质酸酶和尿激酶治疗透明质酸动脉栓塞大鼠腹壁皮肤缺血性病变的效果,比较添加硝普钠和不添加硝普钠溶栓的差异。方法2020年7月至2021年3月,在潍坊医学院医学实验动物中心,雄性SD大鼠40只,经左侧腹壁浅动脉注射10μl透明质酸,制作大鼠左侧腹壁浅动脉栓塞皮肤缺血模型,分为对照组(生理盐水联合5%葡萄糖注射液溶栓注射)、实验A组(透明质酸酶联合5%葡萄糖注射液溶栓注射)、实验B组(透明质酸酶联合尿激酶溶栓注射)、实验C组(透明质酸酶、尿激酶联合硝普钠溶栓注射);术后0 min、3、5、7 d观察皮瓣变化。比较7 d各组大鼠皮瓣平均未灌注面积百分比差异。结果术后7 d,对照组、实验A、B、C组皮瓣平均未灌注面积百分比分别为(100.00±0.00)%、(44.68±7.90)%、(34.01±8.77)%和(24.12±4.58)%。实验C组皮瓣坏死结痂面积百分比低于实验A组(P<0.05),实验C组皮瓣坏死结痂面积百分比低于实验B组(P<0.05),实验B组皮瓣坏死结痂面积百分比低于实验A组(P<0.05)。HE染色显示,添加硝普钠后HA栓子大小及密度明显降低。结论静脉内用硝普钠联合透明质酸酶和尿激酶能够有效改善透明质酸动脉栓塞引起的皮瓣缺血,增加组织灌注,缩小皮瓣坏死面积。

Objective To explore the effect of intravascular sodium nitroprusside(SNP)combined with hyaluronidase(HAase)plus urokinase(UK)in treating rat abdominal wall skin flap ischemia caused by HA induced artery embolism,and to compare the difference between thrombolysis with and without addition of sodium nitroprusside.Methods Forty male Sprague-Dawley rats were injected with 10μl of hyaluronic acid(HA)into the left inferior epigastric arteries,constructing the superficial epigastricl artery skin flap ischemic model in rats.The rats were randomly divided into four groups:a control group,and experimental groups A,B and C.Control and experimental groups A,B and C were treated with the following solutions 45 minutes after hyaluronic acid injection:physiological saline plus glucose was injected into the rats(control group);hyaluronidase(HAase)plus glucose injection was injected into the rats(experimental group A),hyaluronidase(HAase)plus urokinase(UK)was injected into the rats(experimental group B),hyaluronidase(HAase),urokinase(UK)plus sodium nitroprusside were injected into the rats(experimental group C).The changes of flaps were observed at 0 min,3 days,5 days and 7 days after operation.The difference of the area percentage of unperfused flap in the four groups was compared 7 days after operation.This study was carried out from July 2020 to March 2021 in the Medical Laboratory Animal Center of Weifang Medical University.Results The unperfused area of flaps for the control group,experimental groups A,B and C were(100.00±0.00)%,(44.68±7.90)%,(34.01±8.77)%and(24.12±4.58)%,respectively.In the experimental group C,the scabby necrosis area was smaller than that of the experimental group A(P<0.05);in the experimental group C,the scabby necrosis area was smaller than that of the experimental group B(P<0.05);in the experimental group B,the scabby necrosis area was smaller than that of the experimental group A(P<0.05).HE staining revealed that size and density of the embolus was significantly decreased after the addition of sodium nitroprusside.Conclusions Sodium nitroprusside combined with hyaluronidase and urokinase can effectively improve the ischemia of the flap caused by HA induced artery embolism,increase the tissue perfusion,and reduce the necrotic area of the flap.