哌啶并[2,3-b]哌嗪类衍生物3g的体内抗血栓活性研究

Study of the In Vivo Antithrombotic Activity of Piperidine[2,3-b]Piperazine Derivatives 3g

摘要: 目的：探究哌啶并[2,3-b]哌嗪类衍生物3g体内抗血小板聚集和抗血栓作用。方法：选用SD大鼠，采用比浊法考察3g进入大鼠体内离体抗血小板聚集活性；选用昆明小鼠，腹腔注射角叉菜胶建尾部血栓模型，根据小鼠黑尾情况及黑尾长度，求算尾部血栓抑制率来考察3g对小鼠尾部血栓形成的抑制作用；选用昆明小鼠，测定3g进入体内后的出血时间，考察其对凝血功能的初步影响；最后，根据以上实验结果探究哌啶并[2,3-b]哌嗪类衍生物3g体内抗血栓活性。结果：体内抗血小板聚集活性良好，与空白组的5分钟内最大血小板聚集率(43.16 ± 3.16)%相比，高剂量组(14.25 ± 4.54)%、中剂量组(17.09 ± 4.76)%和低剂量组(21.31 ± 3.18)%的聚集率均显著下降，且抑制作用呈剂量依赖性；对角叉菜角诱导小鼠尾部血栓形成具有较强的抑制作用，与模型组相比，3个剂量下均显著缩短血栓长度，血栓抑制率分别为高剂量39.81%、中剂量30.89%、低剂量19.82%；小鼠尾部出血时间实验结果显示：跟空白组相比，化合物在3个治疗剂量下，出血时间无显著差异(P < 0.05)。结论：哌啶并[2,3-b]哌嗪类衍生物3g进入体内后经过生物转化具有跟体外一致的抗血小板聚集活性，并且对角叉菜胶诱导的小鼠尾部血栓具有较强的抑制作用。

Abstract: Objective: To explore the antiplatelet aggregation and antithrombotic effect of 3g of the combined [2,3-b]piperazine derivatives. SD rats were selected, and the anti-platelet aggregation activity of 3g into the rat in vitro was investigated by turbidimetric method; Kunming mice were injected with carrageenan to build tail thrombosis model. According to the black tail and the length of black tail, the inhibition rate was calculated to investigate the inhibitory effect of 3g on tail thrombosis; Kun-ming mice were selected to determine the bleeding time of 3g into the body to determine its initial effect on coagulation function; Finally, we explore the antithrombotic activity of 3g of the combined [2,3-b]piperazine derivatives from the above experimental results. Results: The anti-platelet ag-gregation activity in vivo was good, compared with the maximum platelet aggregation rate within 5 minutes of the blank group (43.16 ± 3.16)%, the high-dose group (14.25 ± 4.54)%, the middle-dose group (17.09 ± 4.76)% and the low-dose group (21.31 ± 3.18)% of the aggregation rates were sig-nificantly decreased, and the inhibition was dose-dependent; Compounds 3g has inhibitory effect in tail thrombosis in mice. Compared to the model group, the thrombus length was significantly shortened at all three doses. The thrombus inhibition rate was 39.81% high dose, 30.89% medium dose and 19.82% low dose. The results of the tail bleeding time in mice showed that: compared with the blank group, the bleeding time of compounds at 3 therapeutic doses was not significantly dif-ferent (P < 0.05). Conclusion: Piperidine[2,3-b]piperazine derivatives 3g has anti-platelet aggrega-tion activity consistent with in vitro, and has a strong inhibitory effect on tail thrombosis in mice.