他克莫司通过下调NFATc2抑制大鼠球囊损伤后颈总动脉内膜增生

发布时间：2018-04-05 19:37

  本文选题：他克莫司　切入点：血管内膜　出处：《中国新药与临床杂志》2015年12期

【摘要】：目的观察他克莫司对大鼠球囊损伤后血管壁内膜增生的干预作用并探讨其机制。方法将27只健康雄性SD大鼠随机分成假手术组、球囊损伤模型组及他克莫司组(n=9),除假手术组外,其余大鼠建立颈总动脉球囊损伤模型。他克莫司组大鼠灌胃给予他克莫司(1 mg·kg~(-1)),假手术组和球囊损伤模型组大鼠灌胃给予相同体积的双蒸水,每日1次,连续给药14 d。最后一次给药后24 h,取损伤侧血管行HE染色,计算管腔面积、血管内膜面积(NIA)及内膜面积/中膜面积(NIA/MA);real-time PCR法检测肿瘤坏死因子(TNF)-α和白细胞介素(IL)~(-1)βm RNA表达,免疫组化法检测增殖细胞核抗原(PCNA)、活化T细胞核因子(NFAT)c2蛋白在血管壁中的表达。结果与假手术组相比,球囊损伤模型组管腔面积明显减小,NIA、NIA/MA增加,TNF-α和IL~(-1)βm RNA表达增高,PCNA、NFATc2蛋白表达增高(P0.01)。与球囊损伤模型组相比,他克莫司组管腔面积增加,NIA增厚程度减轻,NIA/MA减小,TNF-α和IL~(-1)βm RNA的表达降低,PCNA、NFATc2蛋白的表达降低(P0.05或P0.01)。结论他克莫司可明显抑制血管内膜过度增生,其机制可能与其下调血管壁NFATc2蛋白和TNF-α、IL~(-1)βm RNA表达有关。
[Abstract]:Objective to investigate the effect of tacrolimus on intimal hyperplasia after balloon injury in rats.Methods 27 healthy male Sprague-Dawley rats were randomly divided into sham operation group, balloon injury model group and tacrolimus group.The rats in tacrolimus group were given tacrolimus 1 mg / kg, and rats in sham operation group and balloon injury model group were given the same volume of double distilled water once a day for 14 days.Immunohistochemical method was used to detect the expression of proliferating cell nuclear antigen (PCNA) and activated T cell nuclear factor (T) -NFATC _ 2 protein in vascular wall.Compared with the balloon injury model group, the lumen area of tacrolimus group increased and the thickness of NIA increased. NIA / MA decreased the expression of TNF- 伪 and ILF-1) 尾 m RNA. The expression of PCNANFATc2 protein decreased (P0.05) or P0.01 (P < 0.05).Conclusion tacrolimus can significantly inhibit intimal hypertrophy, which may be related to its down-regulation of the expression of NFATc2 protein and TNF- 伪 -l) 尾 m RNA.
【作者单位】： 遵义医学院药理学教研室暨基础药理省部共建教育部重点实验室;遵义医学院珠海校区药理学教研室;
【基金】：国家自然科学专项基金(81241142) 教育部“长江学者和创新团队发展计划”(IRT1197) 贵州省科技厅社发攻关计划项目(SY[2010]3055)
【分类号】：R965
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