环孢菌素A对大鼠腹主动脉球囊损伤后内膜增生的抑制作用

Cyclosporine A inhibits intima proliferation of rat abdominal aortas injured by balloon

目的:探讨环孢菌素A对大鼠腹主动脉球囊损伤后内膜增生的影响。方法:雄性SD大鼠36只,随机分为假手术组(n=12)、球囊损伤组(n=12)和环孢菌素治疗组(n=12)。环孢菌素组大鼠行腹主动脉球囊损伤术前3 d开始每天灌喂环孢菌素A 12.5 mg/kg,假手术组和球囊损伤组灌喂等容积的水,直至术后30 d。球囊损伤术后30 d取材,血管组织作HE染色、免疫组化检测钙调神经磷酸酶(CaN)在血管壁中的表达,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和活化T细胞核因子3(NFATc3)的表达变化。结果:球囊损伤后血管壁出现新生内膜,形成的新生内膜厚度不均。环孢菌素治疗组与球囊损伤组相比较,内膜增生减轻,内膜/中膜厚度明显降低(P<0.05)。免疫组化检测血管壁上CaN表达,环孢菌素治疗组明显低于球囊损伤组(P<0.05)。大鼠腹主动脉损伤后,损伤血管壁组织CaN和NFATc3 mRNA表达升高,环孢菌素治疗组与球囊损伤组相比表达明显减少(P<0.05)。结论:环孢菌素A可能通过抑制CaN-NFATc途径减轻球囊扩张术后动脉再狭窄。

AIM： To observe the effect of cyclosporine A on intima hyperplasia of rat abdominal aortas injured by balloon.METHODS： Thirty-six healthy adult male SD rats were randomly divided into 3 groups： sham group（n=12）,balloon-injured group（n=12） and cyclosporine A treatment group（n=12）.From the 3rd day before injury to the 30th day after injury,the rats in cyclosporine A treatment group were treated with cyclosporine A at a dose of 12.5 mg/kg everyday,while the rats in sham group and balloon-injured group were fed with the same volume of water.On the 30th day after injury,the specimens were obtained from the rats.HE staining and immunohistochemistry were used to measure the expression level of calcineurin（CaN） in arterial wall.Pathological changes of the arterial wall were observed under light microscope.The expression of CaN and nuclear factor 3 of activated T-cells（NFATc3） in the abdominal aortas was detected by the technique of real-time PCR.RESULTS： Intimal hyperplasia was observed in balloon-injured rats.The neointima was not uniform in thickness on the 30th day.The thickness of the intimal layers and the ratio of the intimal to the medial layers in cyclosporine A group were obviously lower than those in balloon group（P0.05）.Immunohistochemistry revealed that calcineurin expression increased after balloon injury,but the expression of calcineurin in cyclosporine A group was obviously decreased as compared with balloon group（P0.05）.The results of real-time PCR showed that the mRNA expression of calcineurin and NFATc3 in cyclosporine A group was significantly lower than that in balloon-injured group（P0.05）.CONCLUSION： Cyclosporine A attenuates restenosis by suppressing the CaN-NFATc signaling pathway.