活血及活血解毒配伍中药对急性心肌梗死大鼠模型血小板活化、炎症反应及凝血状态的影响

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目的观察活血及活血解毒配伍中药对急性心肌梗死大鼠血小板活化、炎症反应及凝血状态的影响。方法 100只SD雄性大鼠,按随机数字表法分为假手术组、模型组、活血组、活血解毒组、倍他乐克组,每组20只。活血组给予芎芍胶囊(0.39 g/kg),活血解毒组给予芎芍胶囊(0.39 g/kg)加黄连胶囊(0.135 g/kg),倍他乐克组给予倍他乐克片(2.25 mg/kg),假手术组及模型组均给予等量生理盐水,连续干预3周。末次灌胃后,利用在体结扎冠状动脉前降支法建立急性心肌梗死模型,假手术组只穿线不结扎。造模24 h后处死动物,用ELISA法检测血清中β-血小板球蛋白(β-TG)、血小板α颗粒膜蛋白-140(GMP-140)、11去氢血栓烷B2(11-DH-TXB2)、纤维蛋白肽A(FPA),抗凝血酶Ⅲ(AT-Ⅲ)、D-二聚体(DD)及肿瘤坏死因子α(TNF-α)指标,采用RT-PCR法检测大鼠心肌TNF-αmRNA表达。结果与假手术组比较,模型组血小板活化指标(β-TG、11-DH-TXB2及GMP-140)均明显升高(P<0.01);与模型组比较,除倍他乐克组GMP-140外,各给药组血小板生化指标均有明显降低(P<0.01,P<0.05),且活血解毒组β-TG、11-DH-TXB2水平优于倍他乐克组(P<0.05),而活血解毒组11-DH-TXB2亦优于活血组(P<0.05)。凝血状态显示:与假手术组比较,AMI模型组高凝状态明显,FPA、D-D水平升高(P<0.05,P<0.01),抗凝的ATⅢ降低(P<0.01);与模型组比较,各给药组FPA水平明显降低(P<0.01),活血及活血解毒组ATⅢ明显升高(P<0.01),活血解毒组D-D明显降低(P<0.01),且活血解毒组3项指标均优于倍他乐克组(P<0.05)。TNF-α血清含量及心肌TNF-αmRNA表达显示:与假手术组比较,模型组血清TNF-α含量及心肌组织TNF-α表达明显升高(P<0.05,P<0.01);与模型组比较,活血解毒组不仅TNF-α的血清含量降低(P<0.01),同时心肌组织中TNF-α的基因表达也明显改善(P<0.01)。结论活血解毒中药可以从抗血小板活化、改善高凝状态及抑制炎症反应等不同作用环节发挥疗效,明显优于单纯的活血化瘀中药。 Objective To observe the effects of traditional Chinese medicine of activating blood circulation, promoting blood circulation and detoxifying on platelet activation, inflammatory reaction and blood coagulation status in rats with acute myocardial infarction. Methods 100 male Sprague-Dawley rats were randomly divided into sham-operation group, model group, Huoxue group, Huoxue Jiedu group and Betaloc group, with 20 rats in each group. The rats in Huoxue group were treated with Xiongshao capsule (0.39 g / kg), Xuanwu decoction group (0.39 g / kg) and Huanglian capsule (0.135 g / kg) / kg), sham-operation group and model group were given the same amount of saline, continuous intervention for 3 weeks. After the last gavage, the model of acute myocardial infarction was established by ligation of the anterior descending coronary artery in vivo, and the sham-operated group was not ligated by threading. Animals were sacrificed 24 hours after the model was established. Serum levels of β-thromboglobulin, GMP-140, 11-DH-TXB2 ), Fibrinopeptide A (FPA), antithrombin Ⅲ (AT-Ⅲ), D-dimer (DD) and tumor necrosis factor α (TNF- TNF-α mRNA expression. Results Compared with the sham operation group, the platelet activation indexes (β-TG, 11-DH-TXB2 and GMP-140) in model group were significantly increased (P <0.01) (P <0.01, P <0.05), and the levels of β-TG and 11-DH-TXB2 in blood-clearing and detoxifying groups were better than that of Betaloc (P <0.05) , While blood-promoting detoxification group 11-DH-TXB2 also better than activating blood group (P <0.05). Compared with the sham group, the hypercoagulability state, FPA and DD levels in AMI model group were significantly increased (P <0.05, P <0.01), and ATⅢ in anticoagulant group was decreased (P <0.01) The levels of FPA in each group were significantly decreased (P <0.01), AT Ⅲ in blood and promoting blood circulation and detoxification were significantly increased (P <0.01), and DD in Huoxue detoxification group was significantly lower (P <0.01) In betatrex group (P <0.05). Compared with the sham operation group, the level of TNF-α in serum and the level of TNF-α in myocardial tissue in model group were significantly increased (P <0.05, P <0.01), compared with model group The serum level of TNF-α was significantly lower in the Huoxue Jiedu group than that in the control group (P <0.01). Meanwhile, the gene expression of TNF-α in myocardium was also significantly improved (P <0.01). Conclusion Huoxue Jiedu traditional Chinese medicine can exert its curative effect in different aspects such as anti-platelet activation, hypercoagulable state and inflammatory reaction, which is obviously better than that of traditional Chinese medicine of promoting blood circulation and removing blood stasis.
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