他克莫司对截肢大鼠肺损伤的保护作用研究

Exploring Tacrolimus （FK506） on its protective action against lung injuries induced by traumatic amputation in rat

目的观察他克莫司fFK506）对截肢大鼠肺损伤的保护作用并初步探讨其作用机制。方法制备大鼠左后肢截肢模型，将健康雄性Wistar大鼠70只随机分为10组：正常对照组，截肢后1h、2h,4h,6h、12h、24h、48h、72h组及FK506干预组。测定肺组织CaN—amRNA表达、MPO、MDA浓度，观察肺组织HE染色病理变化。结果肺脏CaN—amRNA水平正常组为（O．909±0．040），截肢后1h开始升高至（1．193±0．744），6h达峰值（2．272±1．250），（P〈0．05）后逐渐下降；MDA浓度正常组为（3．571±0．226），1h开始升高至（4．696±0．856），6h达峰值（5．109±0．832）（P〈0．01），后逐渐下降，72h降至正常；MPO浓度正常组为（0．223±0．041），1h后即出现显著升高至（0．325±0．073）（P〈0．01），之后一直处于高位水平。FK-506干预组与截肢后6h组比较CaN—amRNA水平（0．279±0．056）（P〈0．01）、MDA浓度（4．103±0．526）（P〈0．05）及MPO浓度（0．277-＋0．047）（P〈0．01）均明显下降。病理切片见：截肢术后6h肺泡间隔增宽，充血水肿、炎细胞浸润明显，FK-506干预后减轻。结论FK506可有效降低截肢大鼠肺损伤的严重程度，其机制可能与抑制氧自由基、抑制炎症反应有关。

Objective To observe the FK506 protective action against lung injuries induced by traumatic amputation in rats, and investigate its mechanism. Methods The rat models with amputation were prepared. Seventy male Wistar rats were randomly divided into 10 groups, control group, 8 post-operation groups, including one hour, two-hour, four-hour, six-hour, twelve-hour, twenty-four-hour, seventy-two-hour, and group FK506, with seven rats in each group. The CaN-αmRNA levels, MPO and MDA concentrations of lung tissue were detected. The lungs＇ histopathology changes were observed. Results The CaN mRNA level in the control group was 0.909±0.040, increased after the operation; the highest level reflected at six-hour group with 2.272± 1.250 （P 〈0.05） followed by a decrease; the MDA concentration in control group was 3.571 ±0.226, also increased after the operation; the highest was 5.109±0.832 （P 〈0.01） at six-hour group; the MPO concentration was 0.223±0.041 in control group; there was an obvious increase in one-hour group with 0.325±0.073 （P 〈0.01） and kept at a high ievel afterword. Comparing with six-hour group, the CaN-amRNA level 0.279＋0.056 （P〈0.01）, MDA4.103 ±0.526 （P 〈0.05） and MPO 0.277 ± 0.047 （P 〈0.01） concentration were all markedly decreased in FK506 group. Histopathology reflected the lung injuries emerged in six-hour group while FK506 group was relieved. Conclusions FK506 is considered as being effective in relieving lung injuries in amputation rats through inhibiting the free oxygen radicals and inflammatory response.