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氢溴酸普拉格雷醋酸合物的抗血栓作用研究
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| 篇名： | 氢溴酸普拉格雷醋酸合物的抗血栓作用研究 |
| TITLE： | |
| 摘要： | 目的：探讨氢溴酸普拉格雷醋酸合物的抗血栓作用及其可能机制。方法：以硫酸氢氯吡格雷为阳性对照，采用全自动血栓检测仪测定低、中、高剂量氢溴酸普拉格雷醋酸合物和盐酸普拉格雷（均为0.05、0.5、5 mg/kg，以普拉格雷计）作用后大鼠体外血栓长度、湿质量和干质量，采用酶联免疫吸附测定法检测低、中、高剂量氢溴酸普拉格雷醋酸合物（0.05、0.5、5 mg/kg，以普拉格雷计）作用后大鼠血小板中环磷酸腺苷（cAMP）的含量；用角叉菜胶诱发小鼠体内血栓形成，以游标卡尺测量低、中、高剂量氢溴酸普拉格雷醋酸合物和盐酸普拉格雷（均为0.2、2、20 mg/kg，以普拉格雷计）预处理后小鼠的黑尾长度及相对平均长度。结果：经中、高剂量氢溴酸普拉格雷醋酸合物和盐酸普拉格雷作用后，大鼠体外血栓长度均较正常对照组显著缩短，血栓湿质量和干质量均较正常对照组显著减轻（P＜0.05或P＜0.01）；氢溴酸普拉格雷醋酸合物各剂量组大鼠上述指标与盐酸普拉格雷同等剂量组、氢溴酸普拉格雷醋酸合物高剂量组大鼠上述指标与硫酸氢氯吡格雷组比较，差异均无统计学意义（P＞0.05）。经中、高剂量氢溴酸普拉格雷醋酸合物作用后，大鼠血小板中cAMP的含量均较正常对照组显著升高（P＜0.05或P＜0.01）。经中、高剂量氢溴酸普拉格雷醋酸合物和盐酸普拉格雷预处理后，小鼠的黑尾长度及相对平均长度均较模型组显著缩短（P＜0.01），且氢溴酸普拉格雷醋酸合物高剂量组和盐酸普拉格雷高剂量组小鼠上述指标均显著短于硫酸氢氯吡格雷组（P＜0.05）；而氢溴酸普拉格雷醋酸合物各剂量组小鼠上述指标与盐酸普拉格雷同等剂量组比较，差异均无统计学意义（P＞0.05）。结论：氢溴酸普拉格雷醋酸合物可显著缩短大鼠体外血栓长度，减轻血栓湿质量和干质量，缩短角叉菜胶致小鼠的黑尾长度及相对平均长度，且其作用与盐酸普拉格雷相当。上述作用可能与氢溴酸普拉格雷醋酸合物上调血小板中cAMP的含量有关。 |
| ABSTRACT： | OBJECTIVE： To investigate the antithrombotic effects of prasugrel hydrobromide acetic acid compound. MEHTODS： Using clopidogrel bisulfate as positive control， automatic thrombus detector was used to detect length， wet weight and dry weight of in vitro thrombus in rats after treated with low-dose， medium-dose and high-dose of prasugrel hydrobromide acetic acid compound and prasugrel hydrochloride （0.05， 0.5， 5 mg/kg， by prasugrel）. The content of cAMP in platelet of rats was determined by ELISA after treated with low-dose， medium-dose and high-dose of prasugrel hydrobromide acetic acid compound （0.05， 0.5， 5 mg/kg， by prasugrel）. The in vivo thrombus in mice was induced by carrageenan. The black tail length and the relative length were measured with vernier calipers after pre-treated with low-dose， medium-dose and high-dose of prasugrel hydrobromide acetic acid compound and prasugrel hydrochloride （0.2， 2， 20 mg/kg， by prasugrel）. RESULTS： After treated with medium-dose and high-dose of prasugrel hydrobromide acetic acid compound and prasugrel hydrochloride， the length of in vitro thrombus was shortened significantly， wet weight and dry weight were decreased significantly， compared with normal control group （P＜0.05 or P＜0.01）. There was no statistical significance in above indexes between prasugrel hydrobromide acetic acid compound groups and corresponding prasugrel hydrochloride groups， between prasugrel hydrobromide acetic acid compound high-dose group and clopidogrel bisulfate groups （P＞0.05）. After treated with medium-dose and high-dose of prasugrel hydrobromide acetic acid compound， the content of cAMP in platelet of rats was increased significantly， compared with normal control group （P＜0.05 or P＜0.01）. After pretreated with medium-dose and high-dose of prasugrel hydrobromide acetic acid compound and prasugrel hydrochlorde， black tail length and the relative length were shortened significantly， compared with model group （P＜0.01）， and above indexes of prasugrel hydrobromide acetic acid compound high-dose group and prasugrel hydrochloride high-dose group were significantly shorter than clopidogrel bisulfate group （P＜0.05）. There was no statistical significance in above indexes between prasugrel hydrobromide acetic acid compound groups and corresponding prasugrel hydrochloride groups （P＞0.05）. CONCLUSIONS： Prasugrel hydrobromide acetic acid compound can significantly decrease the length， wet weight and dry weight of in vitro thrombus， and shorten the black tail length and the relative length of mice. Prasugrel hydrobromide acetic acid compound and prasugrel hydrochloride have similar antithrombotic effects. The above effects are performed by up-regulating the content of cAMP in platelet with prasugrel hydrobromide acetic acid compound. |
| 期刊： | 2018年第29卷第22期 |
| 作者： | 郑晓霞，程艳玲，刘纯，黄艳妮 |
| AUTHORS： | ZHENG Xiaoxia，CHENG Yanling，LIU Chun，HUANG Yanni |
| 关键字： | 氢溴酸普拉格雷醋酸合物；盐酸普拉格雷；硫酸氢氯吡格雷；抗血栓；抗血小板聚集；体外；体内 |
| KEYWORDS： | Prasugrel hydrobromide acetic acid compound； Prasugrel hydrochloride； Clopidogrel bisulfate； Antithrombus； Antiplatelet aggregation； in vitro； in vivo |
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