烟雾吸入伤大鼠肺组织α_1-AR的变化与哌唑嗪保护作用的实验研究

Experimental study of the changes of α_1-adrenergic receptor in lung tissues after smoke inhalation injury in rats and the protective effects of prazosin on pulmonary smoke inhalation injury

目的 探讨α1肾上腺素受体 (α1-AR)在烟雾吸入伤大鼠肺组织变化与哌唑嗪对烟雾吸入伤的保护作用。方法 采用大鼠烟雾吸入伤模型致伤大鼠 ,干湿重法测定肺组织含水量 ,伊文斯蓝法测定肺微量血管通透性 (PMVP) ,放射受体分析法测定肺组织α1-AR的变化。结果 烟雾吸入致伤后大鼠PMVP增大 ,2h达显著水平 ,6h达高峰 ,2 4h仍显著高于正常 ;肺含水量伤后 2h明显升高 ,6h达非常显著水平 ,2 4h达高峰 ;肺组织α1-AR密度于烟雾致伤后 2、4、6及 2 4h显著升高 ,但亲和力除伤后 2h升高之外 ,无明显变化。相关分析显示 ,肺组织α1-AR密度的升高与PMVP增大呈显著正相关。腹腔给予α1-AR阻断剂哌唑嗪 0 5、1 5及 3 0mg/kg能明显降低PMVP及肺水含量 ,减轻肺损伤。结论 大鼠烟雾吸入性肺损伤的发病机制与α1-AR密度升高有关 ,哌唑嗪对烟雾吸入伤具有一定保护作用。

Objective To investigate the changes of α 1-adrenergic receptor(α 1-AR) in lung tissues after smoke inhalation injury and the protective effects of prazosin on pulmonary smoke inhalation injury in rats. Methods The smoke inhalation injury model in rats was prepared with routine method, the lung water content and the pulmonary microvascular permeability (PMVP) were determined by use of the wet-dry weight ratio and Evans blue method respectively. The α 1-AR in rat's lung tissues was measured with radioreceptor analysis. Results The PMVP was evidently enlarged at 2th hour, peaked at 6th hour and still larger than that of normal control rats at 24th hour after smoke inhalation injury. The lung water content was increased significantly at 2 and 4th hour, and peaked at 24th hour. At 2,4,6 and 24th hour, the density of α 1-AR was elevated significantly, but the affinity of α 1-AR in rat's lung tissues was elevated only at 2th hour after smoke inhalation injury. There was a significant positive correlation between the increase of the density of α 1-AR and the enlargement of PMVP. In addition, prazosin 0.5, 1.5, and 3.0 mg/kg ip reduced the PMVP and the lung water content obviously, and attenuated the lung demage. Conclusion The mechanisms of pulmonary smoke inhalation injury in rats are related to the elevation of the density of α 1-AR in lung tissues, and prazosin has some protective effects on pulmonary smoke inhalation injury.