川芎嗪对犬CABG后LAD平滑肌细胞表达Ⅷ胶原和p53的影响  

Intervention of ligustrazine on expressions of VIII collagen and p53 in vascular smooth muscle cells of canine LAD after CABG in dogs

作　　者：何维来[1] 周汝元[1] 陈如坤[2] 

机构地区：[1]安徽医科大学第一附属医院心脏外科,安徽合肥230032 [2]浙江大学医学院附属第二医院心胸外科,浙江杭州310009

出　　处：《第四军医大学学报》2008年第5期394-398,共5页Journal of the Fourth Military Medical University

基　　金：安徽省十五攻关课题(G321009)

摘　　要：目的:探讨川芎嗪(LG)对冠状动脉旁路移植术(CABG)后冠脉左前降支(LAD)血管平滑肌细胞表达VIII型胶原和p53反应性改变的影响.方法:45只健康杂交犬体质量(17.9±2.2)kg,结扎LAD近段制作局部冠状动脉狭窄模型后,将存活的28只犬分为LG组(n=10),维拉帕米(VR)组(n=10)和生理盐水(CN)对照组(n=8),三组均行CABG,手术前后对各组犬施加不同的药物干预.经犬右心耳抽血检测不同时段血浆NO含量变化;术后2wk切取局部LAD,用Western Blot法检测LAD组织匀浆VIII型胶原和p53蛋白表达,并用免疫组化方法观察两种分子在局部的原位表达情况.结果:吻合血管后血浆NO含量60min时,LG组下降至(77.7±2.4)μmol/L,VR组为(69.3±1.5)μmol/L,CN对照组为(62.4±2.1)μmol/L,LG组与其他两组相比较差异具有统计学意义(P<0.05);三组正常LAD的组织匀浆表达VIII型胶原和p53水平低,VR组和CN对照组的血管吻合处远段LAD表达VIII型胶原增加比川芎嗪组明显,而LG组p53表达增加比其他两组明显.免疫组化方法检测表明:三组的吻合处远段血管片段局部VIII型胶原表达明显增加,LG组明显弱于其他两组,LG组可以检测到p53表达,而其他两组吻合后损伤血管的p53无明显表达.结论:LG可抑制CABG后血管内皮损伤及LAD平滑肌细胞表达VIII胶原反应性的上调和促进p53表达,表明其可能具有防治CABG术后再狭窄的作用.AIM： To explore the interventional effect of lignstrazine on the expressions of type Ⅷ collagen and p53 by vascular smooth muscle cells （VSMCs） of canine left anterior descending artery （LAD） after coronary artery bypass graft （CABG）. METHODS： Forty-five healthy mongrel dogs weighing （ 17.9± 2.2 ） kg were ligated at the near part of the LAD to make local coronary artery stenosis models. The 28 surviving dogs were divided into 3 groups ： lignstrazine group （ n = 10）, verapamil group （n = 10） and control group （n = 8）, and all animals underwent CABG surgeries. The 3 groups were given different drug intervention. We measured the changes of plasm NO of blood samples collected from right atrial appendage in different time. Local LAD harvested 2 wk after surgery were detected for the expressions of type Ⅷ collagen and p53 in VSMCs by Western Blotting and immunohistochemistry methods. RESULTS： The content of NO of the 3 groups continually changed with time elapsing after anastomosis. Compared with the content of NO of ligustrazine group descending to （ 77.7±2.4 ） μmol/L in 60 min, the descent of measurement of the other 2 groups [（69.3 ±1.5） μmol/L in verapamil group, （62.4±2.1 ） μmol/L in control group] was significant （P 〈0.05）. Expressions of type Ⅷ collagen and p53 in nomal LAD tissue homogenate by Western Blotting were lower, but after anastomosis, the expression of type Ⅷ collagen in LAD distant from anastomosis site in verapamil group and control group was higher than that of ligustrazine group, while the expression of p53 in ligustrazine group was obviously up-regulated compared with the other 2 groups. The results by immunohistochemistry methods indicated that the expression of type Ⅷ collagen in local impaired LAD tissiue in the 3 groups was obviously up-regulated, and ligustrazine group was lower than the other 2 groups. The expression of p53 could be detected conspicuously in ligustrazine group, but it was not found in the other 2 groups.

关 键 词：冠状动脉狭窄 血管平滑肌细胞 川芎嗪 Ⅷ型胶原 P53 基因表达 

分 类 号：R542.22[医药卫生—心血管疾病] R282.71[医药卫生—内科学]