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

Abstract

Objective To evaluate the effect of dexmedetomidine pretreatment on expression of secretion 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 lipopolysaccharide(LPS)5 mg/kg over 1 min.Dexmedetomidine 10 μg/kg was intravenously infused over 10 min starting from 10 min before LPS in group DEX.At 10 min 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 ultrastructure of Clara cells(with a transmission electron microscope)and for determination of CC16 expression in bronchioles(by immunohistochemistry). Results Compared with the baseline at 10 min before LPS injection, the expression of CC16 in bronchioles was significantly down-regulated at 1, 2, 4, 6 and 24 h after LPS injection in group ALI 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 cells in bronchioles were reduced, the secretory granules in the cytoplasm were reduced, and the mitochondria were swollen and deformed after injection of LPS.Compared with group ALI, the expression of CC16 in bronchioles was significantly up-regulated 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. Key words: Dexmedetomidine; Lipopolysaccharide; Acute lung injury; Clara cell