右美托咪定预先给药对大鼠内毒素性急性肺损伤时Clara细胞分泌蛋白表达的影响

Effect of dexmedetomidine pretreatment on expression of Clara cell secretory protein during endo-toxin-induced acute lung injury in rats

目的评价右美托咪定预先给药对大鼠内毒素性急性肺损伤时Clara细胞分泌蛋白（CC16）表达的影响。 方法健康Wistar大鼠112只，雌雄不拘，8～12周龄，体重250～350 g，采用随机数字表法分为2组（n＝56）：急性肺损伤组（ALI组）和右美托咪定预先给药组（DEX组）。经1 min静脉注射LPS 5 mg/kg制备内毒素性急性肺损伤模型。DEX组于注射LPS前10 min时经10 min静脉输注右美托咪定10 μg/kg。分别于注射LPS前10 min和注射LPS后0.5、1、2、4、6、24 h时处死8只大鼠，取肺组织，光镜下观察病理学结果，透射电镜下观察Clara细胞超微结构，采用免疫组化法测定细支气管CC16表达。 结果与注射LPS前10 min时比较，ALI组注射LPS后1、2、4、6和24 h时、DEX组注射LPS后1、2、4和6 h时细支气管CC16表达下调（P〈0.01），注射LPS后肺小动脉充血、肺泡隔水肿，红细胞渗出和炎性细胞浸润，细支气管Clara细胞减少，胞质内分泌颗粒减少，线粒体肿胀变形；与ALI组比较，DEX组注射LPS后1、2、4、6和24 h时细支气管CC16表达上调（P〈0.01），肺组织病理学损伤减轻，Clara细胞数增多。 结论右美托咪定预先给药减轻大鼠内毒素性急性肺损伤的机制可能与上调CC16的表达有关。

Objective To evaluate the effect of dexmedetomidine pretreatment on expression of se- cretion protein of Clara cell secretory protein （CC16） during endotoxin-induced acute lung injury （ALI） in rats. Methods One hundred and twelve healthy Wistar rats of both sexes, aged 8-12 weeks, weighing 250-350 g, were divided into ALI group （n= 56） and dexmedetomidine pretreatment group （group DEX, n= 56） using a random number table. ALI was induced by intravenously injecting lipopolysaceharide （LPS） 5 mg/kg over 1 min. Dexmedetomidine 10μg/kg was intravenously infused over 10 rain starting from 10 rain before LPS in group DEX. At 10 rain before LPS injection and 0.5, 1, 2, 4, 6 and 24 h after LPS injection, 8 rats were sacrificed and lungs were removed for examination of the pathological changes （ with a light microscope） and ultrastrueture of Clara cells （with a transmission electron microscope） and for deter- mination of CC16 expression in bronchioles （ by immunohistochemistry）. Results Compared with the baseline at 10 rain before LPS injection, the expression of CC16 in bronchioles was significantly down-regu- lated at 1, 2, 4, 6 and 24 h after LPS injection in group ALl and at 1, 2, 4 and 6 h after LPS injection in group DEX （P〈0. 01） , the pulmonary small arterial hyperemia, alveolar septa edema, red blood cell exudation and inflammatory cell infiltration were found, the Clara ceils in bronchioles were reduced, the secretory granules in the cytoplasm were reduced, and the mitochondria were swollen and deformed after in- jection of LPS. Compared with group ALl, the expression of CC16 in bronchioles was significantly up-regu-lated at 1, 2, 4, 6 and 24 h after LPS injection （P〈0.01） , the pathologic changes of lung tissues were significantly attenuated, and the number of Clara cells was increased in group DEX. Conclusion The mechanism by which dexmedetomidine pretreatment reduces endotoxin-induced ALI may be related to up- regulating CC16 expression in rats.