摘要目的:探索羟基红花黄色素A（HSYA）联合透明质酸酶（HAase）能否增强透明质酸（HA）动脉栓塞的治疗效果。方法:32只雄性白色家兔采用随机数字表法分为4组，每组8只，其中A、B、C组为试验组，D组为对照组。建立HA动脉栓塞模型：于兔耳背侧面以中央动脉为轴，距耳根部4.0 cm，蒂宽1.0 cm，切开大小为2.0 cm × 5.0 cm的矩形复合组织瓣（深度达耳腹侧软骨膜），原位连续缝合，自近端向远端分3等分（Ⅰ、Ⅱ、Ⅲ区）；距组织瓣近端1 cm与中央动脉交点为进针点，注入HA 50 μl。在栓塞60 min后，对各组进行治疗。A组：于大腿隐静脉缓慢注入HSYA溶液20 ml（HSYA按10 mg/kg计算用量）；B组：于耳进针点注入HAase溶液0.5 ml（400 U/ml）；C组：于耳进针点注入HAase溶液0.5 ml，大腿隐静脉缓慢注入HSYA溶液20 ml，药物剂量同A、B组；D组大腿隐静脉、耳进针点及A、B组除给药途径的另一注射部位给予等量生理盐水。腿部注药每日1次，共14 d。于术后即刻和第1、7、14天观察组织瓣情况，并拍摄兔耳背侧照和逆光照，计算术后第14天组织瓣成活面积百分比。术后第14天，对兔耳组织瓣Ⅱ区取材，做HE和Masson染色，并检测超氧化物歧化酶（SOD）活力和丙二醛（MDA）含量。符合正态分布计量数据以 ± s表示，多组间比较采用单因素方差分析，采用LSD检验分析两组间差异， P<0.05认为差异有统计学意义。 结果:术后即刻各组组织瓣均呈苍白色。术后第1天，各组远端出现暗淡的缺血区。术后第7天，各组缺血区不同程度坏死、发黑，非坏死区肿胀明显。术后第14天，各组缺血区进一步坏死、发黑、卷曲、边界清；C组最轻，D组最重，A、B组介于其间，A、C组非坏死区基本消肿。HE染色示：D组血管内形成大量血栓，大量炎性细胞浸润；B组次之；A、C两组血栓少见。Masson染色示：C组胶原纤维排列规则；D组大量胶原纤维崩解断裂；A、B组介于其间。A、B、C、D各组组织瓣成活面积百分比分别为（69.87±5.04）%、（85.03±6.58）%、（93.93±4.25）%、（49.22±9.64）%，组间两两比较差异均有统计学意义（ P均<0.05）。A、B、C、D各组SOD活力分别为（49.83 ± 8.08）、（36.65 ± 5.49）、（55.61±7.93）、（22.45±5.47）U/mg prot，除A组与C组差异无统计学意义外，其余组间两两比较差异均有统计学意义（ P均<0.05）。A、B、C、D各组MDA含量分别为（0.77±0.17）、（1.03±0.16）、（0.68±0.12）、（0.41±0.09）nmol/mg prot，除A组与C组差异无统计学意义外，其余组间两两比较差异均有统计学意义（ P均<0.05）。 结论:动物实验条件下，与单独应用HAase相比，HSYA联合HAase能明显增强HA动脉栓塞的治疗效果，增加组织瓣成活面积比例。

abstractsObjective:The aim of this study was to explore whether hydroxysafflor yellow A (HSYA) combined with hyaluronidase (HAase) can enhance the therapeutic effect of arterial embolism caused by hyaluronic acid (HA) .Methods:Thirty-two white male rabbits were randomly divided into four groups, with 8 rabbits in each group, of which group A, B and C were experimental groups and group D was group control. An axial rectangular composite tissue flap sized 2.0 cm × 5.0 cm, with 1.0 cm pedicle width, and 4.0 cm from the root, was designed with the central auricular artery as the long axis on the dorsal side of the ear. The depth of incision reached the ventral perichondrium of the ear, and the flap was sutured continuously in situ and divided into three equal parts (area Ⅰ, Ⅱ, Ⅲ) from the proximal area to the distal area. The proximal end 1 cm to the flap and the central artery was the intersection point, into which 50 μl HA was injected, by which the model of HA arterial embolism was established. Each group was treated after 60 min. Group A: 20 ml solution HSYA was injected slowly into the thigh saphenous vein (the dosage of HSYA is calculated at 10 mg/kg) . Group B: 0.5 ml solution HAase was injected into the central auricular artery (400 U/ml) . Group C: 0.5 ml solution HAase with the same dosage of group B was injected into the central auricular artery and 20 ml solution HSYA with the same dosage of group A was injected slowly into the thigh saphenous vein. Group D and other parts of group A and B were injected with the same dosage of normal saline (NS) . The thigh saphenous veins of all groups were injected with the same dosage of solution once a day for 14 days. Flaps were observed immediately, 1, 7 and 14 days after establishment of hyaluronic acid arterial embolism models of tissue flaps, and dorsal and backlight auricular photographs were taken. On the postoperative 14th day, percentages of survival areas of the flaps were calculated, and samples were taken from areas II of tissue flaps, which were stained by hematoxylin-eosin (HE) and Masson, and were detected the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) . The measurement data conformed to normal distribution was represented as Mean ± SD. Single factor analysis of variance (ANOVA) was used to compare the differences among groups, and head-to-head comparison by LSD test. P <0.05 was considered statistically significant. Results:Tissue flaps of all groups were pale immediately after operation. On the first day after operation, the dark ischemic area appeared at the distal end of each group. On the postoperative 7th day, the ischemic area of each group was necrotic and blackened to varying degrees, and the non-necrotic area swelled obviously. On the postoperative 14th day, the ischemic area of each group was further necrotic, blackened, curled and the boundary was clear. Group C was the best, group D was the worst, and both group A and B were between the two. The swelling of non-necrotic areas in group A and C were basically reduced. HE staining showed that numerous thrombi and inflammatory cells infiltration were formed in group D, and group B was behind it, and thrombi were rare in group A and C. Masson staining showed that collagen fibers were arranged regularly in group C, and abundant collagen fibers were disintegrated and disordered in group D, and both group A and B were between the two. The percentages of survival areas of the flaps in group A, B, C and D were as follows: (69.87 ± 5.04) %, (85.03 ± 6.58) %, (93.93 ± 4.25) % and (49.22±9.64) %. There were statistical differences in pairwise comparison between groups (all P <0.05) . SOD activity of group A, B, C and D were as follows: (49.83±8.08) , (36.65±5.49) , (55.61±7.93) and (22.45 ± 5.47) U/mg prot. Except that group A vs. C, there were statistical differences between groups (all P <0.05) . MDA content of group A, B, C and D were as follows: (0.77±0.17) , (1.03±0.16) , (0.68±0.12) , and (0.41±0.09) nmol/mg prot. Except that group A vs. C, there were statistical differences between groups (all P <0.05) . Conclusions:Under the condition of animal experiment, compared with HAase, HSYA combined with HAase can significantly enhance the therapeutic effect of HA arterial embolism and increase the proportion of survival area of tissue flap.