黄芪甲苷对大鼠颈总动脉内膜增殖、炎症反应及PI3K/Akt/mTOR信号通路的影响  

Effect of astragaloside IV on neointimal hyperplasia,inflammatory re⁃sponse and PI3K/Akt/mTOR signaling pathway in carotid arteries of rats

作　　者：李友乾 尉希清[1] 宋秉春 张洪生[1] 张金国[2] LI Youqian;WEI Xiqing;SONG Bingchun;ZHANG Hongsheng;ZHANG Jinguo(Heart Failure Ward of Cardiology,Affiliated Hospital of Jining Medical University,Jining 272029,China;Coronary Heart Disease Ward 2 of Cardiology,Affiliated Hospital of Jining Medical University,Jining 272029,China)

机构地区：[1]济宁医学院附属医院心内科心力衰竭病区,山东济宁272029 [2]济宁医学院附属医院心内科冠心病二病区,山东济宁272029

出　　处：《中国病理生理杂志》2023年第4期677-683,共7页Chinese Journal of Pathophysiology

基　　金：济宁市重点研发计划项目(No.2018SMNS006);山东省中医药科技发展计划项目(No.2019-0481)。

摘　　要：目的:基于磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路探究黄芪甲苷(ASIV)对球囊损伤后大鼠颈总动脉内膜增殖和炎症反应的作用机制。方法:选用SPF级健康雄性Sprague-Dawley(SD)大鼠24只,12周龄,约280~300 g,适应性喂养3 d,使用球囊损伤法建立大鼠颈总动脉球囊损血管模型,实验共分为4组,假手术(sham)组、模型(model)组、低剂量ASIV(L-ASIV)组和高剂量ASIV(H-ASIV)组,每组6只。L-ASIV给于60 mg·kg^(−1)·d^(−1)的ASIV,H-ASIV给于120 mg·kg^(−1)·d^(−1)的ASIV灌胃治疗,sham组及model组给予相同体积的1%羧甲基纤维素钠灌胃。4周后取大鼠损伤处颈总动脉做石蜡切片,光镜下观察血管腔形态,通过图像分析软件评估管腔面积和内膜增生程度、内膜中膜比值;检测血管组织中磷酸化PI3K(p-PI3K)、磷酸化Akt(pAkt)、磷酸化mTOR(p-mTOR)、增殖细胞核抗原(PCNA)、α-平滑肌肌动蛋白(α-SMA)、细胞间黏附分子1(ICAM-1)、微管相关蛋白1轻链3B(LC3B)和P62的蛋白水平。结果:(1)与sham组相比,model组大鼠颈总动脉内膜显著增殖(P<0.05),经过ASIV干预后内膜增殖程度显著降低(P<0.05)。(2)与model组相比,L-ASIV组和H-ASIV组CD3和CD68表达水平显著降低(P<0.05)。(3)与model组相比,H-ASIV组p-PI3K、p-Akt、p-mTOR、PCNA、ICAM-1和P62蛋白水平显著升高(P<0.05),α-SMA和LC3B蛋白表达水平显著降低(P<0.05)。结论:黄芪甲苷可能通过激活PI3K/AKT/mTOR信号通路抑制血管平滑肌细胞自噬来发挥对球囊损伤后大鼠颈总动脉内膜增殖及炎症的抑制作用。AIM:To investigate the effect of astragaloside IV(ASIV)on the intimal proliferation and inflammatory response in rat common carotid artery after balloon injury.METHODS:Twenty-four healthy,male,SPF-grade Sprague-Dawley(SD)rats(aged 4~6 weeks and weighing approximately 280~300 g)were selected for adaptive feeding for 3 d.The balloon injury method was used to establish a model of balloon-induced damage to the common carotid artery in the rats.The rats were divided into 4 groups:sham group,model group,low-dose ASIV(L-ASIV)group and high-dose ASIV(H-ASIV)group.The rats in L-ASIV group were given 60 mg·kg^(−1)·d^(−1) ASIV,those in H-ASIV group were given 120 mg·kg^(−1)·d^(−1) ASIV,and those in sham and model groups were given the same volume of 1%sodium carboxymethyl cellulose by gavage.After 4 weeks,the common carotid artery was collected from the injured rats for paraffin sectioning,and the lumen morphology was observed under a light microscope.The lumen area,degree of intimal hyperplasia and intimal medium membrane ratio were evaluated with image analysis software.The protein levels of phosphorylated phosphatidylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-Akt),phosphorylated mammlian target of rapamycin(p-mTOR),proliferating cell nuclear antigen(PCNA),α-smooth muscle actin(α-SMA),intercellular adhesion molecule-1(ICAM-1),microtubule-associated protein 1 light chain 3B(LC3B)and P62 in the vascular tissue were detected.RESULTS:(1)The intimal proliferation of the common carotid artery in model group was significantly greater than that in sham group(P<0.05),and the degree of intima proliferation was significantly reduced after ASIV intervention(P<0.05).(2)The expression levels of CD3 and CD68 in L-ASIV and H-ASIV groups were significantly lower than that in model group(P<0.05).(3)Compared with model group,the protein levels of p-PI3K,p-Akt,p-mTOR,PCNA,ICAM1 and P62 were significantly increased in H-ASIV group(P<0.05),whileα-SMA and LC3B protein expression levels were significantly decrease

关 键 词：黄芪甲苷 内膜增生 球囊损伤 自噬 PI3K/Akt/mTOR信号通路 

分 类 号：R541.4[医药卫生—心血管疾病] R363.2[医药卫生—内科学]