芎芍胶囊对动脉粥样硬化兔血管平滑肌细胞增殖的影响

作者	单位
徐凤芹	中国中医科学院西苑医院
徐浩	中日友好医院全国中西医结合心血管病中心
刘剑刚	中国中医科学院西苑医院
陈可冀	中国中医科学院西苑医院

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中文摘要:

目的研究芎芍胶囊对实验性兔动脉粥样硬化(AS)血管平滑肌细胞(VSMC)增殖的影响,并探讨其可能的机制。方法采用4F.Fogarty导管剥脱损伤腹主动脉内皮后继喂高脂饲料的方法,复制兔节段性AS模型。术后随机分为8组,即模型3天组、2周组、6周组,单纯内皮损伤组,普罗布考组,芎芍胶囊小剂量组、大剂量组及假手术组。除假手术组及单纯内皮损伤组外均予高脂饲料喂养,采用增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)免疫组化方法分析腹主动脉病变最明显处新生内膜中VSMC增殖活性,透射电镜观察VSMC的表型转变及采用放射免疫法测定血浆血管紧张素Ⅱ(AngⅡ)的水平,观察药物对其的影响。结果内皮损伤喂食高脂饲料3天(模型3天组),血浆AngⅡ水平逐渐升高,6周时(模型6周组)与假手术组比较差异显著(P<0.01);芎芍大剂量组血浆AngⅡ水平明显降低,与模型6周组比较差异显著(P<0.05);普罗布考组及芎芍小剂量组AngⅡ水平亦有降低的趋势,但与模型6周组比较差异无统计学意义。PCNA免疫组化染色结果显示,假手术组血管中未见PCNA阳性表达细胞,模型3天组内膜中有少量表达,模型2周组内膜细胞的阳性表达最多,模型6周组内膜明显增厚,但PCNA阳性表达有所下降,药物组阳性反应细胞数均明显减少,尤以芎芍大剂量组为著,与模型6周组比较,差异有统计学意义(P<0.05,P<0.01)。透射电镜观察结果显示,假手术组兔腹主动脉中膜VSMC形态正常,模型3天组VSMC形态基本正常;但模型2周组,中膜VSMC已向内膜迁移;模型6周组,VSMC内脂质颗粒增多,有较大的空泡,细胞间胶原纤维增生更加明显,单纯内皮损伤组VSMC亦呈合成型改变,各用药组损伤血管新生内膜中合成型VSMC较模型6周组少,其中,普罗布考组与芎芍小剂量组VSMC内仍有较多脂滴,细胞间有较多胶原纤维增生,而芎芍大剂量组VSMC形态已基本正常,细胞间只有少量胶原纤维增生。结论芎芍胶囊可明显降低血浆AngⅡ水平,抑制VSMC的迁移、增殖,从而抑制AS的发生发展。

英文摘要:

Objective To study the effects of Xiongshao Capsule(XSC)on the proliferation of vascular smooth muscle cells(VSMC)in rabbits with experimental atherosclerosis(AS),and to explore its possible mechanisms.Methods Rabbit’s fractional AS model was established by denuding and injuring the endodermis of abdominal aorta with 4F·Fogarty catheter,followed with feeding of high cholesterol forage.The animals were randomly divided into 8 groups,the model groups of 3 days,2 weeks and 6 weeks after modeling(Group A,B and C);the single endothelium injury group(Group D),the probucol treated group(Group E),the low-dose and high-dose XSC treated groups(Group F and G)and the sham operative group(Group N).All were fed with high fat forage except those in Group N and D.The proliferative activity of neogenetic SMC at abdominal aorta with the most obvious pathological changes was analyzed by proliferating cell nuclear antigen immunohistochemical method;the VSMC phenotypic modulation was detected by transmission electron microscope(TEM),and the level of plasma angiotensin(AngⅡ)was measured by radioimmunoassay.And the effects of treatment on them were observed as well.Results The plasma Ang Ⅱ level elevated gradually in Group A,and showed significant difference as compared that between Group C and Group N(P<0.01);as compared with Group C,that in Group G was reduced significantly(P<0.05);a reducing tendency was shown in Group E and F,but the difference of them with Group C was insignificant.Immunohistochemical dyeing showed that PCNA positive expressing cell was not found in the blood vessels of Group N,few was seen in Group A,while the upmost positive expression was shown in Group B,as for in Group C,significantly thickened endomembrane appeared,but the PCNA positive expression dropped.Number of PCNA positive cells reduced significantly(P<0.05)in the drug treated groups,especially in Group G,showing significant difference as compared with that in Group C(P<0.05,P<0.01).TEM demonstrated normal shaped VSMC of aortic medial tunica in Group N,basically normal in Group A,but in Group B,migration of VSMCs into intima was found,as for in Group C,abundant lipid granules and bigger vacuoles appeared in VSMCs with markedly proliferated intercellular collagenous fibers.Synthetic transformation could also be found in Group D.The transform VSMCs in neogenetic endothelium was fewer in the drug treated groups than that in Group C.Morphology of VSMC was basically normal in Group G,with few intercellular collagenous fiber proliferation,while in Group E and F,many lipid droplets in VSMC and lot of collagenous fibers proliferation in intercellular space still retained.Conclusions XSC can prevent the genesis and development of AS through significantly lowering the plasma Ang Ⅱ level and inhibiting the migration and proliferation of VSMC.

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