RNAⅢ抑制肽/磷酸胆碱基细胞膜仿生药物涂层的血液相容性(英文)

Blood biocompatibility of RNAⅢ inhibiting peptide/bioinspired phosphorylcholine-based cytomembrane coating

背景:课题组在国内首次合成了葡萄球菌抑制剂RNAⅢ抑制肽,并制备了RNAⅢ抑制肽/磷酸胆碱基细胞膜仿生药物涂层。目的:评价RNAⅢ抑制肽/磷酸胆碱基细胞膜仿生药物涂层的血液相容性。设计、时间及地点:随机对照动物实验,于2005-10/2007-10在解放军总医院临床药理研究所及医学动物实验中心完成。材料:成年普通级健康新西兰大白兔30只,由解放军总医院动物实验中心提供。方法:将洁净的316L不锈钢片浸渍于5g/L的四元共聚物四氢呋喃和质量分数10%的RNAⅢ抑制肽混合溶液中,获得稳定的聚合物涂层,按1cm2/mL在37℃无菌条件下用生理盐水浸提72h,制得浸提液原液;加入同体积的无菌生理盐水制得50%浸提液。选择溶血实验、凝血实验、血小板聚集实验,测定凝血酶原时间和活化部分凝血酶时间、观察RNAⅢ抑制肽/磷酸胆碱基细胞膜仿生药物涂层对兔白细胞、红细胞和血小板的影响。主要观察指标:红细胞溶血率,凝血时间、凝血酶原时间、活化部分凝血酶时间,白细胞、红细胞和血小板数量,血小板聚集情况。结果:溶血实验结果显示浸提液原液和50%浓度浸提液的溶血率分别为3.08%和1.88%,两者的溶血率均<5%,符合医用生物材料的溶血实验要求。凝血实验结果表明浸提液原液和50%浓度浸提液对兔凝血时间无明显影响,对各时间点兔凝血酶原时间和活化部分凝血酶时间均无明显作用,对兔白细胞、红细胞和血小板数量无明显影响,对兔血小板聚集无明显影响。结论:实验数据表明,国内首次合成的RNAⅢ抑制肽/磷酸胆碱基细胞膜仿生药物涂层具有良好的血液相容性。

BACKGROUND： Staphylococci inhibitor, RNAIII inhibiting peptide, has been firstly synthesized in China, while RNAIII inhibiting peptide/bioinspired phosphorylcholine-based cytomembrane coating （RIP/PC） has been also prepared. OBJECTIVE： To evaluate the blood compatibility of RIP/PC. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at Institute of Clinical Pharmacologic Research and Medical Animal Experimental Center of General Hospital of Chinese PLA from October 2005 to October 2007. MATERIALS： A total of 30 healthy adult New Zealand rabbits were provided by Animal Experimental Center of General Hospital of Chinese PLA. METHODS： The 316L stainless steel was dip into a mixture of 5 g/L quaternionic copolymer tetrahydrofuran and 10% RNAIII inhibiting peptide to obtain stable polymer coating, which was extracted at density of 1 cm2/mL in saline at 37 ~C for 72 hours to get 100% eluent. The same volume of saline was added to make 50% eluent. The effects of RIP/PC on leukocytes, erythrocytes, and blood platelet of rabbits were detected via measuring prothrombin time and activated thrombin time during hemolysis test, hemagglutinatin test, and blood platelet aggregation test. MAIN OUTCOME MEASURES： Hemolytic ratio of erythrocytes, clotting time, prothrombin time, activated thrombin time, amounts of leukocytes, erythrocytes, and blood platelet, as well as blood platelet aggregation. RESULTS： Hemolysis test showed that the hemolytic ratio was 3.08% and 1.88% of 100% and 50% eluent, respectively; both the hemolytic ratios were 〈 5%, suggesting being coincidence with hemolytic requests of biological materials. The hemagglutinatin test showed that both 100% and 50% eluent did not have any effect on clotting time, prothrombin time, activated thrombin time, amounts of leukocytes, erythrocytes, and blood platelet, as well as blood platelet aggregation. CONCLUSION： The firstly synthesized RIP/PC has a good biocompatibility.