背景:RT-Q膜为乳酸-透明质酸新型共聚物,其既有透明质酸的多种生物功能、良好的柔韧性、生物相容性,又具有聚乳酸的易加工性及遇水成膜性.目的:考察RT-Q膜对颈外静脉出血大鼠模型的止血效果,评估在肌肉组织局部使用后的组织相容性.设计:随机对照动物实验. 单位:四川大学华西药学院药理教研室,生药教研室. 材料:选用雄性Wistar大鼠130只,鼠龄6周,体质量170~210 g.其中80只用于止血效果的评价,另外50只用于生物相容性实验.实验过程中对动物的处置符合动物伦理学标准.实验目的物成分为DL-乳酸-透明质酸、α-氰基丙烯酸酯、丙酮(溶剂)、氟利昂(抛射剂)的RT-Q气雾剂和成分为丙酮与氟利昂(抛射剂)的附加剂气雾剂均由四川大学华西药学院药剂教研室提供(批号均为20050311).α-氰基丙烯酸酯医用胶由北京瞬康医用胶科技发展有限公司生产(批号20050930).方法:①止血实验:随机将80只大鼠分为4组:RT-Q膜组、氰基丙烯酸酯胶组、附加剂组及阴性对照组,每组20只.动物麻醉后于分离的一侧颈外静脉剪一约0.6 cm切口使其出血,并立即以消毒纱布擦拭创面,纱布移开瞬间迅速喷RT-Q气雾剂1次,或附加剂气雾剂1次,或α-氰基丙烯酸酯医用胶0.15 mL,而后覆上纱布,阴性对照组则擦拭创面后直接覆上纱布让其自然止血,记录止血时间,计算出血量(止血后纱布重量-使用前重量).②局部组织相容性实验:随机将大鼠50只大鼠分为A、B两组.A组30只,采用同体左右侧自身对比法,即麻醉大鼠并行后肢外侧肌肉横切术,拉开肌层,左侧喷附加剂气雾剂1次,右侧喷RT-Q膜气雾剂1次.B组20只,在两后肢外侧造成与A组相同的伤口,不给药.分别于术后1~7,15,23,30 d,取创口处标本,苏木精-伊红染色,光镜下做病理组织学检查.观察膜对伤口愈合的影响、自身降解情况及对周围组织是否产生毒性反应.主要观察指标: 止血实验:止血时间, 出血量;局部组织相容性实验:伤口愈合, 生物降解, 对周围组织的毒性. 结果: 大鼠130只均进入结果分析. RT-Q膜的局部组织相容性:病理组织学检查结果显示,RT-Q膜对伤口愈合既无促进也无延迟性影响,形成的膜于术后15 d开始降解,三四周完全吸收,对周围组织无毒性影响.RT-Q膜的局部止血作用:RT-Q膜组应用后的止血时间和出血量比阴性对照组和附加剂组明显减少(P < 0.01),RT-Q膜组与瞬康医用胶组间比较,差异无显著性意义 (P > 0.05). 结论:RT-Q医用生物膜的局部止血效果显著,与α-氰基丙烯酸酯医用胶相当;同时具有局部组织相容性好的特点.%BACKGROUND: RT-Q medical biomembrane, the novel copolymer synthesized from lactic acid and hyaluronic acid, not only possesses the advantages of hyaluronic acid, such as multiple biological functions, excellent flexibility and biocompatibility, but also has the merits of polylactic acid fragments to be easily processed and transformed to membrane when encountering water. OBJECTIVE: To investigate the hemostatic effect of RT-Q medical biomembrane in rat external jugular vein hemorrhage model, and to evaluate its histocompatibility by locally applying it to rat muscle. DESIGN: Randomized controlled animal trial.SETTING: Department of Pharmacology, Department of Pharmacognosy, West China School of Pharmacy, Sichuan University.MATERIALS: 130 male Wistar rats aged 6 weeks, weighing 170-210 g, were selected. Eighty rats were used for evaluation of hemostatic effect, and the other fifty were used in biocompatibility experiment. Animal intervention met the animal ethical standard. RT-Q aerosol composed of DL-lactic acid and hyaluronic acid, α-cyanoacrylate, acetone (solvent), freon (propellant) and excipient aerosol composed of acetone and freon (propellant) (Batch number 20050311) were provided by Department of Pharmaceutics, West China School of Pharmacy, Sichuan University.α-cyanoacrylate medical adhesive(SUNCON medical adhesive) (Batch number 20050930) was produced by Beijing Suncon Medical Adhesive Science and Technology Development Co., Ltd. METHODS: Haemostatic effect: Eighty male rats were randomly divided into four groups, served as RT-Q, SUNCON (positive control), excipient group and non-treatment group (negative control), twenty in each group. After anesthesia was induced, external jugular vein of rats was exposed, and an approximately 0.6 cm incision was made to create hemorrhage. The bleeding areas were blotted by antiseptic gauze. After removing the gauze, the bleeding surfaces were immediately treated with RT-Q aerosol in the RT-Q group, excipient aerosol in the excipient group, 0.15 mL SUNCON medical adhesive in the SUNCON group, or no agent in non-treatment group, respectively. Then, injury surfaces were covered by gauze. In the non-treatment group, bleeding was left to naturally stop. Bleeding time and blood loss (gauze weight after hemostasia - that before hemostasia) were determined. Local histocompatibility: Rats were divided into A and B groups. Incision was made in rat post-leg muscle after anesthesia was induced. Left bleeding surfaces were treated with excipient aerosol, and right bleeding surfaces were treated with RT-Q aerosol in group A (n=30). The same incision as the group A was made, but no intervention was performed in the group B (n=20). Tissues were possessed and HE-stained for pathological observation under light microscope at days 1, 2, 3, 4, 5, 6, 7, 15, 23, 30 after the surgery. Effect of biomembrane on wound healing, degradation and toxicity to tissues surrounding injuries were observed. MAIN OUTCOME MEASURES: Bleeding time and blood loss in hemostatic experiment; wound healing, biodegradation and toxicity to tissues surrounding injuries in local histocompatibility experiment. RESULTS: 130 rats were involved in the result analysis. Histopathologic examination showed RT-Q membrane had no effect of promoting or delaying wound healing. Membrane formed by RT-Q aerosol began to degrade on the 15th day, absorbed completely during 3-4 weeks, and had no toxicity to surrounding tissues. Bleeding time and blood loss were reduced in the RT-Q group than in the non-treatment group and the excipient group (P < 0.01). There was no significant difference between the RT-Q group and the SUNCON group (P > 0.05).CONCLUSION: RT-Q medical biomembrane as α-cyanoacrylate medical adhesive has significant hemostatic effects on topical bleeding, and possesses good histocompatibility.
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