Protective effect of ulinastatin against cholestasis-associated lung injury in rats / 第二军医大学学报

ABSTRACT

Objective To observe the inflammatory infiltration and morphological changes of lung after treatment with unlinastatin in cholestatic rats, so as to study the protective effect of unlinastatin on the lung of cholestatic rats. Methods Rat obstructive jaundice models were established by bile duct ligation (n = 48). Ulinastatin (UTI, 100 000 U/kg) was injected intrapertioneally after operation. The lung tissues were collected at day 1, 3, 7, and 14 after operation. The hepatic function and pulmonary pathology were observed after treatment; dry/wet ratio and water content were calculated. The parameters for alveolar capillary permeability, content of myeloperoxidase (MPO), and activity of malondialdehyde (MDA) were also assessed. Expression of TNF-α and IL-β was exammed by immunohistochemical method. Results The serum bilirubin, dry to wet ratio and water content of the lung tissues were not significantly different between UTI group and jaundice group (P> 0. 05). The levels of evans blue dyes (EBD), MPO, and the activity of MDA m UTI group were significantly lower than that in the jaundice group and UTI groups at the same time points (P<0. 05). The pulmonary histology showed alleviated edema, lessneutrophil infiltration and RBC in alveolar space in UTI group compared to jaundice group. The pulmonary expression of and IL- 1β and TNF-α was significantly lower in UTI group than that in jaundice group on day 1 and day 14 (P<0. 01). Conclusion Uiinastatin can inhibit pulmonary expression of pro-inflammatory cytokines TNF-α and IL-1β and decrease MPO activity and MDA levels in bile duct-ligated rats, thus improving the permeability of the pulmonary capillary membrane in obstructive jaundice rats and decreasing the pulmonary inflammatory reactions.