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目的研究川芎嗪注射液与阿司匹林、氯吡格雷联用抗家兔血栓形成的作用。方法按照体重将健康日本大耳白兔随机分为7组:空白组对照A、B组,低、高2个剂量中药对照组、联合A、B组,每组6只。空白组给予等容积0.9%NaCl,对照A组给予阿司匹林5.13 mg·kg~(-1),对照B组给予氯吡格雷3.85mg·kg~(-1),低、高2个剂量(川芎嗪注射液6.54,26.16 mg·kg~(-1))中药对照组,联合A、B组(中药对照高剂量组分别加对照A、B组)。川芎嗪注射液耳缘静脉给药10 d以及阿司匹林、氯吡格雷灌胃给药7 d在最后1天给药1 h后,心脏取血,通过体外血栓形成仪测定血栓长度、湿重;通过血小板聚集仪测定在血小板活化因子(PAF)诱导下对血小板聚集率的影响;通过酶联免疫吸附试剂盒测定血清血小板活化因子(PAF)、P-选择素、血小板因子-4(PF-4)的含量。结果联合B组的血栓长度为(7.4±4.6)cm,与空白组的(22.8±2.3)cm比较,差异有统计学意义(P<0.01)。对照A、B组和高剂量中药对照组及联合A、B组的血栓湿重分别为(0.31±0.04),(0.30±0.05),(0.35±0.14),(0.28±0.08),(0.16±0.07)g,与空白组的(0.55±0.10)g比较,差异有统计学意义(均P<0.01)。在PAF诱导下,低、高2个剂量中药对照组、联合A、B组的血小板聚集率分别为(43.3±4.7)%,(37.2±4.7)%,(35.5±4.1)%,(35.0±3.2)%与空白组的(52.9±4.4)%比较,差异有统计学意义(均P<0.01)。与低剂量中药对照组比较,联合A、B组血小板聚集率明显降低,差异有统计学意义(P<0.05)。低、高2个剂量中药对照组、联合A、B组的PAF含量分别为(1043±162),(1010±189),(973±159),(959±178)ng·L~(-1),与空白组的(1510±319)ng·L~(-1)比较,差异有统计学意义(均P<0.01)。对照A、B组,低、高2个剂量中药对照组、联合A、B组的P-选择素含量分别为(156±13),(130±21),(101±17),(85±8),(107±18),(107±19)ng·mL~(-1),与空白组的(234±69)ng·mL~(-1)比较,差异有统计学意义(P<0.01)。对照A、B组和高剂量中药对照组及联合A、B组的PF-4含量分别为(148±14),(255±14),(322±69),(242±26),(266±36)ng·mL~(-1),与空白组的(478±91)ng·mL~(-1)比较,差异有统计学意义(P<0.05,P<0.01)。结论川芎嗪注射液与阿司匹林、氯吡格雷联用能起到协同抗血栓形成的作用。
Objective To study the effect of tetramethylpyrazine injection combined with aspirin and clopidogrel against thrombosis in rabbits. Methods According to body weight, healthy Japanese white rabbits were randomly divided into 7 groups: blank control group A, B group, low and high dose Chinese medicine control group, combined with A, B group, 6 in each group. The blank group was given 0.9% NaCl, the control group A was given aspirin 5.13 mg · kg -1, while the control group B was given clopidogrel 3.85 mg · kg -1, low dose and high dose (Ligustrazine Injection of 6.54,26.16 mg · kg -1) Chinese medicine control group, combined with A, B group (Chinese medicine control high-dose group were added to control A, B group). Ligustrazine injection ear vein administration for 10 days and aspirin, clopidogrel gavage for 7 days on the last day after administration of 1 h, the heart blood, thrombosis thrombus measured by thrombus length and wet weight; by Platelet aggregation was used to measure the platelet aggregation rate induced by platelet activating factor (PAF). Serum platelet activating factor (PAF), P-selectin and platelet factor-4 (PF-4) were measured by enzyme linked immunosorbent assay Content. Results The length of thrombus in group B was (7.4 ± 4.6) cm, which was significantly different from that in group B (22.8 ± 2.3) cm (P <0.01). The thrombus wet weights in control A, B group and high dose control group and A, B group were (0.31 ± 0.04), (0.30 ± 0.05), (0.35 ± 0.14), (0.28 ± 0.08), (0.16 ± 0.07) g, compared with the blank group (0.55 ± 0.10) g, the difference was statistically significant (P <0.01). Under the PAF induction, the platelet aggregation rates in the two groups of low and high doses of traditional Chinese medicine and the combination of A and B groups were (43.3 ± 4.7)%, (37.2 ± 4.7)%, (35.5 ± 4.1)% and (35.0 ± 3.2%) compared with that of the blank group (52.9 ± 4.4)%, the difference was statistically significant (all P <0.01). Compared with the low-dose traditional Chinese medicine control group, the platelet aggregation rate in group A and group B was significantly lower, with significant difference (P <0.05). The levels of PAF in the two groups of low dose and high dose of Chinese traditional medicine control group were (1043 ± 162), (1010 ± 189), (973 ± 159), (959 ± 178) ng · L -1 ) Compared with the control group (1510 ± 319 ng · L -1), the difference was statistically significant (both P <0.01). The levels of P-selectin in control group A, B group, low dose and high dose group were (156 ± 13), (130 ± 21), (101 ± 17) and (85 ± 8, 107 ± 18 and 107 ± 19 ng · mL -1, respectively, compared with that of the control group (234 ± 69 ng · mL -1) (P < 0.01). The content of PF-4 in control A, B group and high-dose traditional Chinese medicine control group and combination A and B group were (148 ± 14), (255 ± 14), (322 ± 69), (242 ± 26) ± 36 ng · mL -1, compared with that of the blank group (478 ± 91) ng · mL -1, the difference was statistically significant (P <0.05, P <0.01). Conclusion Ligustrazine injection combined with aspirin and clopidogrel can play a synergistic antithrombotic effect.