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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。
PURPOSE: The pathological basis of stenosis after vascular injury is neointimal hyperplasia. This study was designed to investigate the effect of survivin and IL-18 on the neointimal hyperplasia after carotid artery injury in rats. Curcumin can reduce the expression of survivin and serum IL-18, Endometrial hyperplasia. Methods: Fifty-six male SD rats were randomly divided into sham operation group, balloon injury group and curcumin treatment group. Establishment of carotid artery injury model in rats. Sham operation group, balloon injury group with the same amount of saline gavage. Curcumin treatment group with 100 mg.kg-1.d-1 gavage. The injured carotid arteries were harvested on days 3, 7, 14 and 28 respectively. The expression of survivin and PCNA protein and mRNA in injured blood vessels were detected by immunohistochemistry and real-time PCR. The levels of IL-18 in serum were detected by enzyme-linked immunosorbent assay (ELISA). Results: The levels of IL-18 in the curcumin-treated group were significantly lower than those in the injury group at 3, 7, 14 and 28 days (P <0.05). Survivin mRNA expression in curcumin treatment group was significantly lower than that in injury group at 7, 14 and 28 days after curcumin treatment (P <0.05), and The expression in 14 and 28 d groups was higher than that in sham-operated group (P <0.05). The mRNA expression of PNCA in curcumin treatment group was significantly higher than that in sham operation group, and was lower than that in injury group at the 7th, 14th and 28th days. Conclusion: Survivin participates in remodeling process after vascular injury and promotes neointimal formation and cell proliferation. Curcumin down-regulates survivin expression and inhibits neointimal hyperplasia. Inflammatory factor IL-18 is expressed early at high levels after vascular injury. Curcumin inhibits the expression of IL-18 and inhibits the inflammation.