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纳米自组装肽作为液体栓塞剂在大鼠动脉瘤模型中的应用 被引量:1

Nanofiber self-assembly peptide as an embolic agent in a rat aneurysm model
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摘要 背景:使用液体栓塞剂栓塞动脉瘤是治疗动脉瘤的一种有效的方法。理想的栓塞剂应具有无毒,组织相容性好,并能有效诱导相应的细胞向材料内生长而达到永久性栓塞动脉瘤的特性。目的:探讨纳米自组装材料RADA16-Ⅰ在大鼠颈总动脉瘤中作为液体栓塞剂的可行性。设计、时间及地点:随机对照动物实验,于2008-03/09在四川大学华西医院科技园完成。材料:RADA16-Ⅰ粉末由上海波泰生物公司合成,醋酸纤维素聚合物购自国药集团化学试剂有限公司。方法:①体外实验:流变仪频率扫描测量短肽10g/L RADA16-Ⅰ水溶液与PBS等体积混合前后的流变学特性。②动物手术:15只Wistar大鼠随机分为3组,10g/L RADA16-Ⅰ组,醋酸纤维素聚合物组,假手术组各5只。麻醉后,小心剥离右侧颈总动脉,并向颈总动脉结扎处2mm近心端注入RADA16-Ⅰ或醋酸纤维素聚合物溶液。假手术组只结扎动脉,不进行栓塞治疗。主要观察指标:①应用TA Instruments Advantage软件分析10g/L RADA16-Ⅰ流变学特性。②术后14d取右侧颈总动脉,制备切片进行苏木精-伊红染色和Masson染色;同时10g/L RADA16-Ⅰ组进行抗平滑肌α-actin抗体免疫组织化学检测。结果:①加入PBS的10g/L RADA16-Ⅰ水凝胶更接近标准的弹性体行为。②假手术组大鼠颈总动脉血管壁明显增厚;醋酸纤维素聚合物组血管壁变薄,管腔内为呈粉色(苏木精-伊红染色)或蓝色(Masson染色);RADA16-Ⅰ组血管壁增厚,血管壁新生内膜细胞向管腔内生长,栓塞材料降解,长入动脉瘤管腔的细胞主要为α-actin阳性的血管平滑肌细胞。结论:RADA16-Ⅰ作为一种液体栓塞剂是可行的。 BACKGROUND: Endovascular embolization with liquid materials has been identified as a useful therapy for aneurysms. The materials with little toxicity, good biocompatibility, and the ability to induce effective cellular response within the vessels are ideal in the treatment of aneurysms. OBJECTIVE: To investigate the feasibility of RADA16- [ (Ac-RADARADARADA RADA-NH2), a nanofiber scaffold material as an embolic agent, in a rat aneurysm model. DESIGN, TIME AND SETTING: Randomized, controlled, animal experiment. The study was performed at Science Park, West China Hospital, Sichuan University between March and September 2008. MATERIALS: RADA16- 1 powder was synthesized by Shanghai Bootech Bioscience & Technology Co., Ltd.; cellulose acetate polymer (CAP) was purchased from Sinopharm Chemical Reagent Co., Ltd. METHODS: g〉Experiment in vitro: The frequency sweep rheological test of 10 g/L RADA16- 1 with or without the phosphate buffer solution (PBS) was performed. (2)Animal surgery: 15 female Wistar rats were randomly divided into 3 groups: 10 g/L RADA16- 1 group, CAP group and sham surgery group with 5 animals in each group. Under anesthesia, the right carotid was carefully exposed, RADA16- 1 or CAP were injected into the common carotid artery (CCA) to induce carotid aneurysm. The sham surgery group only underwent arterial ligation but not embolism treatment. MAIN OUTCOME MEASURES: 〈0TA Instruments Advantage Software was used to analyze the rheological properties of 10 g/L RADA16-1 with or without PBS. (2)The embolized CCAs were harvested 14 days after surgery, followed by HE staining and Masson staining. α smooth muscle actin, the marker in the vascular smooth muscle, in 10 g/L RADA16- 1 group was immunohistochemically examined. RESULTS: (1)10 g/L RADA16-1with PBS possessed the capability of elastic behavior, similar to standard. (2) According to HE and Masson staining, the vessel walls thickened apparently in the sham surgery group. The vessel walls of the CAP group become thinner and there was pink (HE) or blue (Masson) material in the vessels. In the 10 g/L RADA16-1 group, the vessel walls become thickened, and the neointima cells grew into lumina; moreover, the material was degraded. According to immunohistochemical examination, the majority of neointima cells were vascular smooth muscle cells. CONCLUSION: RADA16- 1 is a potential embolic agent.
出处 《中国组织工程研究与临床康复》 CAS CSCD 北大核心 2009年第21期4073-4076,共4页 Journal of Clinical Rehabilitative Tissue Engineering Research
基金 国家985平台项目~~
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