目的:观察活血化瘀法对颈动脉粥样硬化血管内皮损伤模型大鼠wnt/β-catenin信号通路的影响,探讨其可能的作用机制。方法:32只SD大鼠高脂喂养1个月后,随机取8只作为假手术组(仅切开皮肤),其余大鼠均行颈总动脉球囊损伤术,成膜后再随机分为模型组(n=8只)、活血化瘀中药方中剂量(临床等效量)组(n=8只)和高剂量(临床2倍量)组(n=8只)。从术后第4天开始予以相应药物灌胃治疗(模型组、假手术组灌等量生理盐水),2周后取术侧颈总动脉段,采用实时荧光定量PCR法捡测wnt、Fz D1、AXIN1、GSK-3β、β-catenin、VEGF mRNA基因表达水平。结果:与假手术组比较,模型组wnt、Fz D1、AXIN1、β-catenin、VEGF等mRNA水平降低,差异有统计学意义(P<0.01),经活血化瘀中药方干预后,上述各基因mRNA水平均有不同程度升高,尤其是高剂量组与模型组比较差异有统计学意义(P<0.05~0.01);只有GSK-3βmRNA水平各组无明显差异。结论:活血化瘀法可通过上调wnt/β-catenin信号通路表达,使损伤血管VEGFmRNA基因表达水平上升,提示该法可保护颈动脉粥样硬化血管内皮损伤。Objective: To observe the effect of activating blood and resolving stasis on injuried vascular wnt / β-catenin in carotid atherosclerosis mode rats and its possible mechanism. Methods: After one-month high fat-diet,32 SD rats were randomly divided into sham operation group,model group,middle dose( dose in clinical equivalent) group and high dose of( 2 times the amount of clinical) group. Except for the sham operation group,the other rats underwent carotid artery balloon injury surgery. After 3 days of intraperitoneally administered orally,model group and sham operation group were given equal volume of physiological saline,administered continuously for 14 d. Then the expression of wnt,Fz D1,AXIN1,GSK-3β,β-catenin,VEGF mRNA in injured vascular were analyzed by real-time fluorescence quantitative PCR in all groups. Results: Compared with the sham operation group,the expression of Wnt,Fz D1,AXIN1,β-catenin,and VEGF mRNA levels in model group decreased( P < 0. 01); and after treated by activing blood and resolving stasis therapy,the expression of the above genes increased in different degrees,especially in the high dose group( P < 0. 01 ~ 0. 05); but there was no significant difference among groups on the expression of GSK-3β mRNA. Conclusion: The theapy of activating blood and resloving stasis therapy can increase the expression of VEGF mRNA of balloon injured carotid artery vascular through up-regulating wnt / β-catenin signal pathway,which suggested that it can protect the injured vascular of carotid atherosclerosis.福建省教育厅A类科技项目(编号:JA13165);; 福州市科技计划项目(编号:2012-S-155-1);; 福建中医药大学校管科研项目(编号:X2012018
