依折麦布对糖基化终产物诱导的动脉粥样硬化影响  

Effect of ezetimibe on atherosclerosis induced by advanced glycation end products

作　　者：魏新吉 史敏 夏金青 于万水 WEI Xin-ji;SHI Min;XIA Jin-qing;YU Wan-shui(Department of Pharmacy,Hebi Hospital of Traditional Chinese Medicine,Hebi 456650,China;Department of Cardiology,Hebi Hospital of Traditional Chinese Medicine,Hebi 456650,China;Department of Cardiopulmonary Diseases,Hebi Hospital of Traditional Chinese Medicine,Hebi 456650,China)

机构地区：[1]鹤壁市中医院药学部,河南鹤壁456650 [2]鹤壁市中医院心内科,河南鹤壁456650 [3]鹤壁市中医院心肺科,河南鹤壁456650

出　　处：《中国药物应用与监测》2023年第6期422-426,共5页Chinese Journal of Drug Application and Monitoring

摘　　要：目的:探讨依折麦布(ezetimibe,EZE)对晚期糖基化终产物(advanced glycation end products,AGEs)诱导的动脉粥样硬化的调控机制。方法:购买动脉粥样硬化模型大鼠,使用随机数字法分为模型组和治疗组各10只,治疗组使用EZE治疗8周后,分析两组大鼠主动脉组织变化和蛋白表达情况。将体外培养的大鼠胸主动脉平滑肌细胞(vascular smooth muscle cells,VSMC)分为对照组、AGEs组、EZE组和联合处理组,分析细胞特定蛋白表达水平;钙检测试剂和Von Kossa染色法检测细胞中钙含量;最后检测细胞增殖能力和整合素连接激酶(integrin-lindedkinase,ILK)信号通路。结果:HE染色发现EZE治疗后模型大鼠动脉组织中动脉内膜和中膜变薄。免疫组化染色显示,EZE治疗后动脉中膜α-SMA阳性细胞数量增加,OPN阳性细胞数量减少(P<0.05)。EZE能改善模型大鼠主动脉病理结构,细胞表面α-平滑肌肌动蛋白(α-smoothmuscleactin,α-SMA)升高,骨桥蛋白(osteopontin,OPN)表达降低(P<0.01)。AGEs处理血管平滑肌细胞后,α-SMA表达降低,OPN、碱性磷酸酶(alkaline phosphatase,ALP)和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)表达升高,细胞胞质钙含量增加;联合处理组细胞α-SMA表达升高,OPN、ALP和PCNA表达降低,细胞胞质钙含量降低(P<0.01)。AGEs能激活血管平滑肌细胞ILK/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路,而EZE可显著抑制ILK/mTOR信号通路的激活。结论:EZE能够抑制大鼠血管平滑肌细胞胞质钙生成及向成骨细胞转化,抑制动脉粥样硬化发展,这一作用可能与调控ILK/mTOR信号通路相关。Objective:To study the effect of ezetimibe(EZE)on atherosclerosis induced by advanced glycation end products(AGEs).Methods:The atherosclerotic model rats were purchased and divided into the model group and the treatment group with 10 rats each using random number method.After 8 weeks of EZE treatment in the treatment group,the changes of aortic tissue and protein expression in the two groups were analyzed.The cultured rat thoracic smooth muscle cells(VSMC)were divided into control group,AGEs group,EZE group and combined treatment group,and the expression level of specific protein was analyzed.Calcium content in cells was detected by calcium detection reagent and Von Kossa staining.Finally,cell proliferation capacity and integrin-linked kinase(ILK)signaling pathway were examined.Results:HE staining revealed thinning of the intima and mid-membrane in the arterial tissue of the model rats after EZE treatment.Immunohistochemical staining showed an increase in the number of α-SMA-positive cells and a decrease in the number of OPN-positive cells in the intima-media of the arteries after EZE treatment(P<0.05).EZE improved the pathological structure of the aorta in model rats,with elevated cell surfaceα-smoothmuscleactin(α-SMA)and reduced expression of osteopontin(OPN)(P<0.01).After treatment of vascular smooth muscle cells with AGEs,the expression of α-SMA was decreased,the expression of OPN,alkaline phosphatase(ALP)and proliferating cell nuclear antigen(PCNA)was increased,and the cytoplasmic calcium content of cells was increased;the expression of α-SMA was increased,the expression of OPN,ALP and PCNA was decreased,and the cytoplasmic calcium content of cells was decreased in the co-treated group(P<0.01).AGEs activated the ILK/mammalian target of rapamycin(mTOR)signalling pathway in vascular smooth muscle cells,whereas EZE significantly inhibited the activation of the ILK/mTOR signalling pathway.Conclusion:AGEs play a key role in the occurrence and development of renal atherosclerosis,but EZE can improve the devel

关 键 词：依折麦布 动脉粥样硬化 整合素连接激酶/哺乳动物雷帕霉素靶蛋白 糖基化终产物 血管平滑肌细胞 

分 类 号：R965.3[医药卫生—药理学]