摘要
目的通过体内外试验探讨新型小肽ωKWR抑制血小板聚集效应并进行毒性分析。方法于家兔耳缘静脉采血并分离富血小板血浆(platelet-rich plasma,PRP),检测ωKWR体外抗血小板聚集作用;小鼠肺动脉栓塞试验检测ωKWR体内抗血小板聚集作用;小鼠尾出血模型检测ωKWR对生理性止血的影响;急性、亚急性毒性试验及小鼠骨髓微核试验、小鼠精子畸形试验检测ωKWR对小鼠的急性、致畸、致突变毒性及大鼠的亚急性毒性。结果体外血小板聚集试验显示ωKWR最大有效浓度为40μmol/L;肺栓塞试验显示ωKWR具有良好的抑制体内血小板聚集效果;尾部出血时间显示ωKWR在有效浓度范围内不延长生理性止血时间;毒性试验结果显示ωKWR未见急性毒性;亚急性毒性试验结果显示ωKWR对实验动物各脏器和生化指标无明显影响;骨髓细胞微核试验和小鼠精子畸形试验显示ωKWR对生殖系统无影响。结论新型抗栓小肽ωKWR可抑制病理性的血小板聚集,但对生理性止血无影响。动物毒理学试验提示ωKWR具有较高的安全性。
Objective To investigate the inhibitory effect of a novel small peptideωKWR on platelet aggregation and analyze its toxicity.Methods Blood was taken from ear marginal vein of rabbits,from which platelet-rich plasma(PRP)was isolated to explore the resistance ofωKWR on platelet aggregation in vitro.The antiplatelet aggregation ofωKWR in vivo was evaluated by pulmonary artery embolization experiment in mice.The effect ofωKWR on physiological hemostasis was evaluated via tail bleeding model test.The acute,teratogenic and mutagenic toxicities ofωKWR to mice as well as subacute toxicity to rats were analyzed by acute and subacute toxcity tests,mouse bone marrow micronucleus test and mouse sperm abnormality test.Results Platelet aggregation test in vitro showed that the maximum effective concentration ofωKWR was 40μmol/L.Pulmonary embolism test confirmed good inhibitory effect ofωKWR on platelet aggregation in vivo.Tail bleeding time showed thatωKWR did not extend the physiological hemostasis time within the effective concentration range.Acute toxicity test showed no acute toxicity ofωKWR.Subacute toxicity test showed no significant effect ofωKWR on the organs and biochemical indicators of experimental animals.Mouse bone marrow micronucleus test and mouse sperm abnormality test showed no influence ofωKWR on reproductive system.Conclusion The novel antithrombotic peptideωKWR may inhibit pathological platelet aggregation while has no effect on the physiological hemostasis.Toxicological experiments suggest high safety ofωKWR.
作者
康志明
赵琪
郑锦秀
杨婷
杨利军
杨涛
KANG Zhi-ming;ZHAO Qi;ZHENG Jin-xiu;YANG Ting;YANG Li-jun;YANG Tao(Department of Biochemistry and Molecular Biology,Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)
出处
《中国生物制品学杂志》
CAS
CSCD
2020年第12期1363-1369,1375,共8页
Chinese Journal of Biologicals
基金
山西省重点研发计划(生物医药方面)(201703D111029)
山西省重点研发计划项目(201703D321026-2,201803D31072)资助。
关键词
ωKWR
小肽
血小板聚集
毒理学
ωKWR
Small peptide
Platelet aggregation
Toxicology
