脱氢表雄酮抑制血管内膜增生的体内研究  

Inhibitory Effect of Dehydroepiandrosterone on Vascular Neointima Formation in Mice Intimal Hyperplasia Model

作　　者：张曼莉[1] 张曼娜 陈慧[1] 赵昆[1] 刘芳[1] 刘志宽[1] 佟飞[1] ZHANG Manli;ZHANG Manna;CHEN Hui;ZHAO Kun;LIU Fang;LIU Zhikuan;TONG Fei(Department of Emergency, The Second Hospital of Hebei Medical University, Shijiazhuang (050000), Hebei, China)

机构地区：[1]河北医科大学第二医院急诊科,河北省石家庄市050000 [2]河北医科大学第二医院检验科,河北省石家庄市050000

出　　处：《中国循环杂志》2019年第8期817-822,共6页Chinese Circulation Journal

基　　金：河北省医学科学研究重点课题计划(20180314)

摘　　要：目的:观察脱氢表雄酮(dehydroepiandrosterone,DHEA)对颈动脉结扎诱导的内膜增生和局部血管炎症的抑制作用。方法:采用颈动脉结扎法制备内膜增生模型;30只18~20周龄雄性C57BL/6小鼠随机分为对照组、结扎组和DHEA治疗组[给予DHEA100mg/(kg·d)],每组各10只;对照组小鼠颈动脉不完全结扎,后两组小鼠颈动脉完全结扎。用苏木素-伊红(HE)染色观察内膜增生形态学改变,实时荧光定量PCR(qRT-PCR)、蛋白免疫印迹试验检测增殖细胞核抗原(PCNA)、Krüppel样因子5(KLF5)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的信使RNA(mRNA)和蛋白表达水平。结果:HE染色结果显示,与对照组相比,结扎组颈动脉内膜面积减小,内膜/中膜面积(I/M)比值增高;与结扎组相比,DHEA治疗组颈动脉内膜面积减小,I/M比值降低;以上组间差异均有统计学意义(P均<0.05)。qRT-PCR和蛋白免疫印迹实验结果显示,与对照组相比,结扎组PCNA、KLF5、TNF-α和IL-6的mRNA和蛋白表达均显著上调;而与结扎组相比,DHEA治疗组上述基因的mRNA和蛋白水平均明显降低;上述组间差异均有统计学意义(P均<0.05)。结论:DHEA能抑制颈动脉内膜增生和局部血管炎症,该作用一定程度上可能是通过抑制KLF5的表达来实现的。Objectives:To investigate the inhibitory effect of dehydroepiandrosterone(DHEA) on the vascular neointima formation and local vascular inflammation in an intimal hyperplasia model in mice.Methods:Carotid artery ligation was used to establish the intimal hyperplasia model in male C57 BL/6 mice.Thirty mice aged eighteen to twenty weeks were divided into control group(n=10),model group(n=10) and DHEA treatment group(100 mg/kg/d,n=10).Morphological change of intimal hyperplasia was observed on hematoxylin-eosin staining sections.qRT-PCR and Western blot were performed to detect the expression of PCNA,KLF5,TNF-α and IL-6.Results:The results of hematoxylin-eosin staining showed that the intimal area and the I/M ratio were significantly increased in model group than in control group(both P<0.05),which could be significantly attenuated by DHEA treatment(both P<0.05).qRTPCR and Western blot results showed that mRNA and protein expressions of PCNA,KLF5,TNF-α and IL-6 were significantly upregulated in the model group compared with the control group(all P<0.05),which could be significantly downregulated by DHEA treatment(all P<0.05).Conclusions:DHEA could inhibit vascular neointima formation and local vascular inflammation by inhibiting the expression of KLF5.

关 键 词：脱氢表雄酮 内膜增生 炎症 Krüppel样因子5 

分 类 号：R543[医药卫生—心血管疾病]