CaN-NFATc3途径在大鼠腹主动脉球囊扩张术后再狭窄中的作用

Role of CaN-NFATc3 pathway in abdominal aorta restenosis following ballon dilatation in rats

目的研究钙调神经磷酸酶(CaN)及其下游活化T细胞核因子(NFATc3)在球囊扩张术后再狭窄中的作用,为防治血管再狭窄提供新的理论依据。方法雄性SD大鼠随机分为假手术组(n=12)、球囊组(n=12)、环孢菌素(Cs A)组(n=12)。球囊组大鼠用球囊扩张术损伤腹主动脉;Cs A组大鼠从手术前3d至实验结束,每天灌喂Cs A12.5 mg/(kg.d)-1。球囊损伤术后30 d取材,血管组织作苏木素—伊红(HE)染色、免疫组化检测CaN在血管壁中的水平,光学显微镜观察病理学改变;Rea1 time PCR技术检测血管壁组织中CaN、NFATc3的m RNA表达;Elisa法测定血清MCP-1水平。结果球囊损伤后血管壁出现新生内膜,且厚度不均;Cs A组与球囊损伤组相比较内膜增生、内膜/中膜厚度明显减轻(P<0.05)。与假手术组相比,球囊损伤组血管壁组织CaN蛋白及m RNA表达均明显升高、NFATc3的m RNA表达显著增加,血浆炎症因子MCP-1水平也升高(P<0.05)。Cs A组上述各项指标均显著低于球囊损伤组(P<0.05)。结论 CaN-NFATc3途径参与大鼠球囊损伤术后再狭窄的发生;Cs A通过抑制该通路减轻再狭窄的形成。

Objective To investegate the role of calcineurin（CaN） and its downstream nuclear factor of activated T-cells（NFATc3） in abdominal aorta restenosis following balloon dilatation in rats. Methods SD rats were randomly divided into sham-operated group, balloon group and cyclosporine A（Cs A） group. The rats in the latter two groups were subjected to abdominal aorta injury with balloon dilatation, and those in Cs A group were treated with Cs A at the daily dose of 12.5 mg/kg from 3 days before the surgery to the end of the experiment. Thirty days afer the injury, histological analysis of the arterial wall was carried out with HE staining and immunohistochemistry. The expressions of CaN and NFATc3 in the abdominal aortas were detected with rea1-time PCR, and serum concentration of MCP-1 was determined using enzyme-linked immunosorbent assay. Results Intimal hyperplasia with irregular thickness of the neointima was observed in the aorta of rats with ballon injury. In rats with Cs A treatment, the area of the intimal layers and the ratio of the intimal to the medial layers were obviously lower than those in the balloon injury group（P〈0.05）. Compared to those in the sham-operated group, the expressions of calcineurin protein and m RNA and NFATc3 m RNA in the arterial wall and serum level of MCP-1 increased significantly in the ballon injury group（P〈0.05）. Cs A treatment significantly suppressed aorta restenosis and the alterations of CaN, NFATc3 and serum MCP-1 induced by ballon dilatation（P〈0.05）. Conclusions CaN-NFATc3 signal transduction pathway mediates restenosis of rat abdominal aorta following ballon dilatation, and Cs A can attenuate the restenosis by suppressing this pathway.