蛭龙活血通瘀胶囊对阿司匹林抵抗大鼠模型的干预及机制探讨

Intervention and mechanism of Zhilong Huoxue Tongyu Capsule on aspirin resistance model in rats

目的:建立阿司匹林抵抗(AR)的动物模型,观察蛭龙活血通瘀胶囊对AR大鼠的治疗作用,并探讨其可能机制。方法:采用高脂高糖高盐饲料(普通饲料70.8%,猪油15%,蔗糖10%,胆固醇0.2%,食盐4%),喂养12周,同时9~12周灌胃给药[2.68 mg·(100 g)^(-1)·d^(-1)阿司匹林+3.57 mg·(100 g)^(-1)·d^(-1)布洛芬],以建立AR大鼠模型。血栓弹力图(TEG)评价AR造模情况。造模成功后,分为模型组、蛭龙活血通瘀胶囊治疗组、氯吡格雷治疗组,同时设正常组,按实验计划进行对应药物及蒸馏水灌胃治疗。4周后,检测各组大鼠血脂变化、花生四烯酸(aa)诱导途径的最大幅度MA(aa)值、血栓素B2(TXB2)和6-酮-前列腺素F1a(6-keto-PGF1a)含量、miRNA-126的表达。结果:(1)造模12周后,与正常组比较,模型组大鼠MA(aa)值显著增加(P<0.05)。(2)治疗4周后,与模型组比较,蛭龙活血通瘀胶囊治疗组和氯吡格雷治疗组TC显著降低,HDL显著升高(P<0.05),TG无显著性差异(P>0.05),LDL:蛭龙活血通瘀胶囊治疗组显著降低(P<0.05),氯吡格雷治疗组无显著性差异(P>0.05);MA(aa)值显著降低(P<0.05);TXB2显著降低,6-keto-PGF1a显著升高,TXB2/6-keto-PGF1a显著降低(P<0.05);miRNA-126的表达显著提升(P<0.01)。结论:通过饮食和药物共同作用,实验成功制备了AR大鼠模型。蛭龙活血通瘀胶囊对AR大鼠有较好的治疗作用,其作用机制可能与提高miRNA-126的表达有关。

OBJECTIVE To establish an animal model of aspirin resistance(AR),observe the therapeutic effect of Zhilong Huoxue Tongyu Capsule on AR rat model and explore its possible mechanism.METHODS To establish the AR rat model, the rats were fed with high-fat, high sugar and high salt diet(ordinary diet 70.8%,lard 15%,sucrose 10%,cholesterol 0.2%,salt 4%)for 12 weeks, and gastric irrigation of drugs(2.68 mg/100 g/d Aspirin+3.57 mg/100 g/d ibuprofen)for 9-12 weeks.TEG was used to evaluate the model of AR.After successful modeling, they were divided into model group, Zhilong Huoxue Tongyu capsule treatment group and clopidogrel treatment group.At the same time, the normal group was set up.The corresponding drugs and distilled water were given by gavage according to the experimental plan.After 4 weeks, the changes of blood lipid in rats、the maximum MA(aa)value of arachidonic acid(aa)induction pathway、the content of TXB2and 6-keto-PGF1a and the expression of miRNA-126 were detected.RESULTS(1)After 12 weeks, compared with the normal group, the maximum MA(aa) value in the model group increased significantly(P<0.05).(2)After 4 weeks of treatment, compared with the model group, TC in Zhilong Huoxue Tongyu capsule treatment group and clopidogrel treatment group decreased significantly, HDL increased significantly(P<0.05),TG had no significant difference(P>0.05),LDL:Zhilong Huoxue Tongyu capsule treatment group decreased significantly(P<0.05),clopidogrel treatment group had no significant difference(P>0.05).MA(aa)decreased significantly(P<0.05);TXB2decreased significantly, 6-keto-PGF1a increased significantly, and TXB2/6-keto-PGF1a decreased significantly(P<0.05);The expression of miRNA-126 was significantly increased(P<0.01).CONCLUSION AR model in rats was successfully established through the combined action of diet and drugs.Zhilong Huoxue Tongyu capsule has a good therapeutic effect on AR rats, and its mechanism may be related to increase of the expression of miRNA-126.