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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(P<0.01)。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(P<0.05或P<0.01)。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。
Objective To observe the intervention of tacrolimus on the intimal hyperplasia of vascular wall after balloon injury in rats and its mechanism. Methods Twenty-seven healthy male Sprague-Dawley rats were randomly divided into sham-operation group, balloon injury model group and tacrolimus group (n = 9). The rats in other groups were given carotid artery balloon injury model. Rats in the tacrolimus group were given gavage with tacrolimus (1 mg · kg -1). Rats in the sham operation group and the balloon injury model group were intragastrically given the same volume of double distilled water for 1 Times, continuous administration 14 d. Twenty-four hours after the last administration, HE staining was performed on injured blood vessels to calculate the luminal area, intima-media thickness (NIA) and intima-media area (NIA / MA) The expressions of TNF-α and IL-1β mRNA were detected by immunohistochemistry. The expressions of proliferating cell nuclear antigen (PCNA) and activated nuclear factor kappa B (NF-κB) in vascular wall were detected by immunohistochemistry. Results Compared with the sham operation group, the lumen area of the balloon injury model group decreased significantly, the NIA and NIA / MA increased, the expression of TNF-α and IL-1βmRNA increased and the expression of PCNA and NFATc2 increased <0.01). Compared with balloon injury model group, the area of lumen increased, the extent of NIA thickening, NIA / MA decreased, the expression of TNF-α and IL-1βmRNA decreased, the expression of PCNA, NFATc2 Protein expression decreased (P <0.05 or P <0.01). Conclusion Tacrolimus can significantly inhibit the hyperplasia of vascular intima, which may be related to its downregulation of NFATc2, TNF-α and IL-1β mRNA.