基于基质细胞衍生因子-1α/CXCR4通路研究氯吡格雷对大鼠颈动脉狭窄的改善作用  

Improvement effect of clopidogrel on carotid artery stenosis in rats based on stromal cell-derived factor1α/CXCR4 pathway

作　　者：刘婉丽 谭永辉 郑翼徳 LIU Wan-li;TAN Yong-hui;ZHENG Yi-de(Department of Vascular Surgery,The First People's Hospital of Chenzhou City,Chenzhou,Hunan 423000,China)

机构地区：[1]郴州市第一人民医院血管外科,湖南郴州423000

出　　处：《岭南心血管病杂志》2022年第4期361-366,共6页South China Journal of Cardiovascular Diseases

摘　　要：目的探讨氯吡格雷对大鼠颈动脉狭窄的改善作用及对基质细胞衍生因子-1α(stromal cell-derived fac⁃tor-1α,SDF-1α)/CXCR4通路的影响。方法40只SD大鼠随机分为假手术组、模型组、氯吡格雷低剂量组(3 mg/kg)、氯吡格雷中剂量组(6 mg/kg)、氯吡格雷高剂量组(12 mg/kg),每组8只。除假手术组大鼠仅暴露颈动脉外,其余各组大鼠均利用注射器针头抽拉建立颈动脉狭窄模型,术后3 d按照各组给药剂量进行灌胃处理,连续1周,假手术组及模型组仅灌胃等量0.9%氯化钠溶液。采集各组大鼠血清及颈动脉组织,酶联免疫吸附试验(ELISA)试剂盒检测大鼠血清炎症因子浓度,苏木精-伊红(HE)染色检测各组大鼠颈动脉组织病理变化,酶联免疫检测各组大鼠颈动脉组织中α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)浓度,蛋白免疫印迹法(WB)检测颈动脉组织中SDF-1α/CXCR4通路相关蛋白浓度。结果与假手术组大鼠相比,模型组大鼠血清炎症因子浓度显著升高,颈动脉组织管腔狭窄严重,内膜增厚明显,中膜弹力纤维层混乱,颈动脉组织中α-SMA、SDF-1α、CXCR4蛋白浓度显著升高,差异有统计学意义(P<0.05)。与模型组大鼠相比,氯吡格雷各剂量组大鼠炎症因子浓度显著降低,差异有统计学意义(P<0.05);氯吡格雷各剂量组大鼠颈动脉狭窄、内膜增厚等情况得到缓解,呈现一定的剂量依赖效应,其中氯吡格雷高剂量组效果较优。结论氯吡格雷可显著缓解大鼠颈动脉狭窄,可能是通过抑制SDF-1α/CXCR4通路实现的。Objectives To investigate the improvement effect of clopidogrel on carotid artery stenosis and its influence on stromal cell-derived factor-1α(SDF-1α)/CXCR4 pathway in rats.Methods Forty SD rats were randomly divided into sham operation group,model group,low-dose clopidogrel group(3 mg/kg),medium-dose clopidogrel group(6 mg/kg)and high-dose clopidogrel group(12 mg/kg),with 8 rats in each group.The rats in sham operation group only exposed the carotid artery.The rats in the other groups were used to establish the carotid artery stenosis model by pulling the syringe needle,and given intragastric administration according to the dosage of each group for a week three days after operation.The rats in sham operation group and model group were given the same amount of normal saline by gavage.Serum and carotid artery tissue were collected.The serum concentrations of inflammatory factors were detect⁃ed by enzyme linked immunosorbent assay(ELISA)kit.The pathological changes of carotid artery were detected by hematoxylin eosin(HE)staining.The concentration ofα-smooth muscle actin(α-SMA)in carotid artery tissue was detected by ELISA.The concentration of SDF-1α/CXCR4 pathway related proteins were detected by Western blot(WB).Results Compared with those in sham operation group,the serum concentrations of inflammatory factors in model group significantly increased,the carotid lumen stenosis was serious,the intima thickening was obvious,and the elas⁃tic fiber layer of the media was chaotic,the protein concentrations ofα-SMA,SDF-1αand CXCR4 in carotid artery significantly increased(P<0.05).Compared with those in model group,the serum concentrations of inflammatory fac⁃tors in clopidogrel groups were significantly lower(P<0.05),carotid artery stenosis,intimal thickening and other con⁃ditions were relieved and showed a certain dose-dependent effect,in which the effects of clopidogrel high-dose group were better.Conclusions Clopidogrel can significantly alleviate carotid artery stenosis in rats,which may be achieved by

关 键 词：颈动脉狭窄 基质细胞衍生因子-1Α CXCR4 氯吡格雷 

分 类 号：R543.2[医药卫生—心血管疾病]