透明质酸注射后组织坏死机制的实验研究

Study on mechanism behind of tissue necrosis following injection of hyaluronic acid filler

目的探讨透明质酸注射治疗后发生组织坏死的机制。方法采用新西兰白兔20只(40只兔耳),结扎耳郭前动静脉和其他旁支动静脉,制成以耳中央动脉、静脉为主要血供的兔耳复合组织瓣模型。把兔耳组织瓣模型随机分为A、B、C、D组。A、B、C组分别将透明质酸0.2 ml注射入兔耳根部中央动静脉周围、中央静脉内和中央动脉内;D组切断耳中央动脉作为对照。分别于注射后第1、7、14天观察大体和微循环变化,监测皮温和血氧饱和度,第14天处死动物取耳标本进行组织学检查。结果各组动物均出现不同程度的缺血,A组和D组注射后皮温和血氧饱和度变化与注射前相比差异无统计学意义。B组注射后第1天皮温和血氧饱和度下降,而后逐渐回升,差异有统计学意义(P<0.05);A、B和D组所有兔耳均成活。C组注射后兔耳皮温和血氧饱和度急剧下降,差异有统计学意义(P<0.05);7 d后皮肤相继出现溃疡和坏死。结论透明质酸注入动脉内可以导致远端小动脉栓塞和微循环障碍,可能是组织坏死的主要原因。

Objective To investigate the mechanism of tissue necrosis following injection of hyaluronic acid.Methods Twenty New Zealand white rabbits（40 ears） were used to establish ear complex tissue flap models with blood supply only from the central pair of artery and vein by ligating the anterior pair and other branches.Then the animal models were randomly divided into 4 groups.Group A,B and C were injected with 0.2 ml hyaluronic acid into the periphery of the root portion of the central artery,central vein and central artery,respectively;Group D received cutting and ligation of the central artery（control group）.The visual findings,microcirculation changes,skin temperature and percutaneous oxygen saturation were examined at 1,7,and 14 days after injection.The animals were sacrificed on the 14th day and the ears were studied pathologically.Results All the groups showed different degrees of tissue ischemia.In Group A and D the skin temperature and oxygen saturation were not significantly different before and after injection of hyaluronic acid.The skin temperature and oxygen saturation were decreased one day after injection in Group B,and they gradually increased thereafter（P0.05）.All the ears in Group A,B and D survived.The skin temperature and oxygen saturation in Group C were significantly decreased after injection of hyaluronic acid（P0.05）,and all the ears in Group C developed skin ulceration and necrosis after 7 days.Conclusion Injection of hyaluronic acid into the artery can cause obstruction of distal arterioles and microcirculation disorder,which might be the main cause of skin tissue necrosis.