摘要
目的:血管损伤后管腔狭窄的病理基础是新生内膜的增生。本实验探讨大鼠颈动脉损伤后生存素(survivin)及血清白介素-18(IL-18)促进新生内膜增生的作用;观察姜黄素可通过抑制生存素及血清IL-18的表达,减轻新生内膜的增生。方法:56只雄性SD大鼠,随机区组为假手术组、球囊损伤组、姜黄素治疗组。建立大鼠颈动脉损伤模型。假手术组、球囊损伤组用等量生理盐水灌胃。姜黄素治疗组以100 mg.kg-1.d-1灌胃。损伤后大鼠颈动脉分别在第3,7,14,28天取材。免疫组化法及荧光定量PCR检测损伤血管中生存素、PCNA蛋白及mRNA表达;酶联免疫吸附法(ELISA)检测反应不同时间点的标本血清中IL-18的表达水平。结果:姜黄素治疗组IL-18在3,7,14,28 d的血清中表达明显低于损伤组(P<0.05)。生存素蛋白在姜黄素治疗组7,14,28 d的表达明显低于损伤组的表达(P<0.05);姜黄素治疗组survivin的mRNA表达明显低于损伤组各对应时间点的表达,且14,28 d组表达高于对应假手术组(P<0.05)。姜黄素治疗组PNCA的mRNA表达明显高于假手术组,且在第7,14,28天时低于损伤组对应时间点的表达。结论:生存素参与血管损伤后的重塑过程,促进新生内膜的形成和细胞的增殖。姜黄素可下调生存素表达,抑制新生内膜的增生。炎症因子IL-18在血管损伤后的早期高水平表达;姜黄素抑制IL-18的表达,有抑制炎症的作用。
OBJECTIVE To investigate the role of IL-l8 and survivin（SVV）, a factor of cell proliferation, in lesion forma- tion after vascular injury, and to determine the effect of curcumin on cell proliferation in the model. The other objective of this study was to determine the effect of curcumin on cell proliferation in the model. METHODS Fifty six male SD rats were randomly divided into three groups： sham operation group; vascular injury group; curcumintreated group. Model of carotid artery injury was e,;tablished. The sham operation group and vascular injury group was given intragastric administration of normal saline. Curcurnin was given in curcumintreated group （100 mg.kg ^-1 .day^-1）. Injuried carotid arteries of rat was extracted at 3 d, 7 d, 14 d and 28 d. The expressions of survivin and PCNA proteins in target vessels were assessed by immunohistochemisty method. Fluorescencebased realtime reverse trascription PCR was used for quantifacion of mRNA lever of survivin, PCNA. IL-18 in serum was assessed by enzyme linked immunosorbent assay. RESULTS The expression of serumal IL-18 in all curcumin treated groups was significantly lower than in the vascular injury groups（P〈0. 05）. Survivin protein expressed in 7 d, 14 d,28 d curcumin treated groups was significantly lower than in the vascular injury groups（P%0. 05）. Survivin mRNA expressed in all curcumin treated groups was significantly lower than in the vascular injury groups（P〈0. 05）, and it was higher in 14, 28 d groups than in the sham operation groups. PCNA mRNA expressed in all curcumin treated groups higher than the sham operation groups and significantly lower than in 7, 14,28 d vascular injury groups（P%0. 05）. CONCLUSION Survivin had been implicated in the remodeling response to vascular injury process,and promoted proliferation of neointimal and smooth muscle cells. Curcumin inhabited the proliferation of vascular smooth muscle cells,and down regulated the expression of surviviru Inflammatory factor IL-18 had a high expression level in early stage after balloon injury. Curcumin plays an important role in the inhibition of inflammation in this model.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2012年第7期497-501,共5页
Chinese Journal of Hospital Pharmacy
基金
甘肃省自然科学基金资助项目(编号:1010RJZA101)
