白鲜皮水提物对ApoE-/-小鼠动脉粥样硬化晚期病变形成的影响  

Cortex dictamni inhibits formation of advanced atherosclerotic lesions in ApoE-deficient mice

作　　者：王丽丽[1] 吕新勇[2] 李琳[1] 李志强[1,2] 李彦林[1] 萧伟[2] 许扬[1] 

机构地区：[1]中国医学科学院北京协和医学院药用植物研究所,北京100193 [2]江苏康缘药业股份有限公司,江苏连云港222002

出　　处：《中国药理学通报》2014年第3期64-69,共6页Chinese Pharmacological Bulletin

基　　金：国家"重大新药创制"科技重大专项"十一五"及"十二五"计划课题(No 2011ZX09401-014;2012ZX09103201-012)

摘　　要：目的研究白鲜皮水提物(cortex dictamni aqueous extract,CDAE)对载脂蛋白E基因缺损小鼠主动脉弓粥样硬化晚期病变形成的影响及其机制。方法将40只ApoE-/-小鼠随机分成空白对照组和CDAE高、中、低3剂量组(CDAE3.2、1.6、0.8 g·kg-1),每组10只。从第12周龄开始给药至18周龄。实验结束时测定给药前后总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇水平。取各组小鼠主动脉弓,OCT包埋,每只小鼠制作80张病理切片(厚6μm),计算各组主动脉弓粥样硬化病变的面积。体外实验测定CDAE给药后平滑肌细胞的增殖和迁移能力。结果CDAE给药后可明显减少动脉粥样硬化斑块面积,CDAE中、高剂量组给药后ApoE-/-小鼠动脉粥样硬化病变面积均小于对照组(P<0.05,P<0.01),各给药组血脂水平均有不同程度的下降。体外实验表明,CDAE可明显抑制大鼠血管平滑肌细胞的增殖和PDGF诱导的平滑肌细胞迁移。结论CDAE对ApoE-/-小鼠动脉粥样硬化晚期病变形成具有明显的抑制作用,其作用机制可能与降低血脂水平,抑制平滑肌细胞的增殖和迁移能力有关。Aim To determine whether Cortex dictamni aqueous extract(CDAE) has any effect on the formation of advanced aortic atherosclerotic lesions in ApoE-/- mice and to explore the possible mechanisms involved. Methods 40 female ApoE-/- mice were randomly divided into four groups(n = 10) : the controlgroup,high dose CDAE group,medium dose CDAE group and low dose CDAE group. All animals were fed a high fat diet and the three CDAE groups were orally administered with CDAE at different doses(3. 2 mg·g- 1,1. 6 mg·g- 1,0. 8 mg·g- 1) for 6 weeks from1 2 th to 1 8 th week while the control group got the samevolume of distilled water. At the end of the experiment,the serum levels of lipids including total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C) were determined. The heart and proximal aorta were removed from the mice and then cut directly under and parallel to the aortic cusps and the upper portions were embedded in OCT compound.The samples were cut into a total of 80 sections(6μm)and the size of the atherosclerotic lesion in each aortic section was evaluated. In vivo experiment,MTT assay was used to view proliferation of VSMCs. Cell migration was determined by Transwell assay. Results CDAE administration could distinctly reduce the advanced atherosclerotic lesion size in ApoE-/- mice.Compared with the control group,the atherosclerotic lesions of mid dose and high dose administration groups were significantly reduced(P < 0. 05,P < 0. 01). The blood lipids levels had reduced to some degree in each CDAE administration group. In vivo experiment,CDAE significantly inhibited proliferation and migration capabilities of vascular smooth muscle cells. Conclusions CDAE administration may obviously reduce the advanced lesion size in ApoE-/- mice by reducing the serum lipid levels and inhibiting the proliferation and migration of VSMCs.

关 键 词：白鲜皮 ApoE基因缺损小鼠 动脉粥样硬化 平滑肌细胞 增殖 迁移 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]