The study of Ulinastatin to reduce pulmonary inflammation and oxidative injury in rats with severe heatstroke

Abstract

Objective To investigate the effect of ulinastatin on acute lung injury in rats with severe heatstroke.Methods Fourty-eight rats were randomly (random number) assigned into control group (HS group,n =12),low dose Ulinastatin group (LUTI group,n =12),high dose Ulinastatin group (HUTI group,n =12) and non-thermal group (Sham group,n =12).Rats were prepared with pre-warm chamber to initiate heatstroke.The change of rectum temperature (Tc),heat-rate (HR) and mean arterial pressure (MAP) under heat-stress were recorded.The time-point of heatstroke onset and Tc ＞42 ℃ was observed.Arterial blood samples were draw at 0 min,20 min,40 min and 60 min for testing partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2).Bronchoalveolar lavage fluid (BALF) were collected at 60 min,and the concentrations of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-l β) and interleukin-6 (IL-6) in BALF were measured with enzyme linked immunosorbent assay kit.Lung tissues were harvested for observing pathological change and measuring the expression of iNOS with Western blot test.Results Compared with HS group,the time-point of Tc ＞ 42℃ (P =0.00),severe heat-stroke (P =0.00) and the median of survival time (P =0.00) in LUTI and HUTI groups were significantly increased.At 60min after heat-stress,the level of PaO2 in HS group was much lower than those in other groups (P =0.00).But there were no differences between LUTI and HUTI groups (P =0.91).The value of PaCO2 in HS group was much higher than those in other groups (P =0.00).And the differences between LUTI and HUTI groups were no significant (P =0.79).The concentrations of TNF-α,IL-1β and IL-6 in HS group was the highest in four groups (P =0.00,P =0.04 and P =0.04),followed by LUTI,HUTI and Sham group.The concentrations of proinflammatory cytokine in LUTI were higher than those in HUTI group (P =0.02,P =0.00,P =0.00).Compared with HS group,the pathological injuries were alleviated in LUTI and HUTI group (P =0.00).The expression of iNOS in lung tissue of HS group was strengthened than LUTI and HUTI group (P =0.00),and there was a significant difference between LUTI and HUTI group (P =0.03).Conclusion Ulinastatin improves respiratory dysfunction and the prognosis of severe heatstroke rats through reducing the inflammatory and oxidative injury in lung tissue. Key words: Severe heatstroke ; Ulinastatin; Lung injury; Arterial blood gas ; Bronchoalveolar lavage fluid; Interleukin; Tumor necrosis factor; Inducible nitric oxide synthase