花椒毒酚对大鼠心脏移植物血管病的作用及机制研究  

Effect and Mechanism of Xanthotoxol on Cardiac Allograft Vasculopathy in Rats

作　　者：张鹏 张松林[1] 孙来龙 Zhang Peng;Zhang Songlin;Sun Lailong(Department of Thoracic and Cardiovascular Surgery,Yichang Central People's Hospital,The First College of Clinical Medical Science,China Three Gorges University,Yichang 443003,China)

机构地区：[1]三峡大学第一临床医学院[宜昌市中心人民医院]胸心外科,湖北宜昌443003

出　　处：《巴楚医学》2021年第4期96-101,共6页Bachu Medical Journal

摘　　要：目的:探讨花椒毒酚对大鼠心脏移植物血管病(CAV)的作用及相关机制。方法:以Wistar大鼠为供体,SD大鼠为受体,采用胸主动脉腹腔移植法将大鼠随机分为模型组和药物组(再分为空白对照、7天组、28天组和56天组)。药物组花椒毒酚10 mg/(kg·d)灌胃给药,模型组同剂量生理盐水灌胃。各时间点取出移植动脉,常规行HE染色和免疫组织化学染色,并计算各组细胞粘附分子-1(ICAM-1)、肿瘤坏死因子-α(TNF-α)、α平滑肌肌动蛋白(α-SMA),转化生长因子-β1(TGF-β1)和核因子-κB(NF-κB)/P65表达的平均光密度值。结果:模型组在7天时动脉管壁出现大量炎症细胞浸润,56天时内膜增厚明显,而药物组比同期各模型组炎症细胞浸润明显减少、内膜增厚程度明显减小(均P<0.05);与同期各模型组相比,药物组ICAM-1、TNF-α、TGF-β1、NF-κB/P65的平均光密度值均有不同程度降低,α-SMA均有不同程度升高(均P<0.05)。结论:花椒毒酚能降低大鼠CAV中ICAM-1、TNF-α、TGF-β1的表达,保留部分平滑肌细胞的收缩表型,改善血管形态,缓解病情进展,其作用可能与部分抑制NF-κB/P65活化相关。Objective:To explore the effect and mechanism of xanthotoxol on cardiac allograft vasculopathy(CAV)in rat.Methods:Wistar rats were used as donors and SD rats were used as recipients.The rats were randomly divided into the model group and the drug group followed after artery transplantation.The drug group was then divided into the blank control group,the 7 days group,the 28 days group and the 56 days group according to the time of administration.Rats in drug group were intragastrically administered with xanthotoxol at a dose of 10 mg/(kg·d),while rats in model group were given the same dose of saline.The morphological changes were evaluated using HE staining and immunohistochemical staining,and the mean optical density values of intercellular adhesion molecule-1(ICAM-1),tumor necrosis factor-α(TNF-α),α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1)and nuclear factor-kappa B(NF-κB)/P65 were calculated.Results:In the model group,a large number of inflammatory cells infiltrated into the arterial wall 7 days after operation.The intimal thickening was obviously on 56 days after artery transplantation.In the drug group,the average optical density of ICAM-1,NF-κB/p65,TNF-αand TGF-β1 were significantly decreased,andα-SMA was significantly increased(all P<0.05),when compared to the model groups at the same period.Conclusion:Xanthotoxol can reduce the expression of ICAM-1,TNF-α,and TGF-β1,retain the contraction phenotype of vascular smooth muscle cells,improve the vascular morphology and alleviate progression of CAV in rats,which may be related to the partial inhibition of NF-κB/p65 activation.

关 键 词：花椒毒酚 心脏移植物血管病 慢性排斥 核因子-κB 

分 类 号：R654.2[医药卫生—外科学] R258.5[医药卫生—临床医学]