The Study on the Protection of Siverlestat Sodiom on the Severe Brain Injury Rats with Secondary Lung Injury
|School||Zunyi Medical College,|
|Keywords||sivelestat Sodium neutrophil elastase acute lung injury severe brain injury|
Objective:To investigate the effects of sivelestat sodium (SVLS) by aerosol inhalation after severe brain injury with secondary lung injury, and provide clinical methods and theoretical basis for lung protection of SBI patients. Methods:①he rat models of severe brain injury were made by a Marmarou model.②20 model rats were randomly divided into two groups:group of severe brain injury (group B, n=10) and group of severe brain injury + aerosol inhalation of SVLS (group C, n=10). Rats of group C were treated by aerosol inhalation of SVLS (1.25mg/kg) added to 10ml normal saline,3 times each day and 20 minutes each time. The two groups were sacrificed by taking blood from the arteria carotis at 24 hours after SBI, then taken the required samples of tissues. Control group (group A, n =10) was fed as usual without any treatment.③The water content of the lung was calculated by measuring the wet and dry weight of lung tissue. The levels of NE in BALF and plasma, IL-8 in BALF were measured by ELISA. The expression of NE in lung tissues was determined by Real-time RT-PCR. The albumin concentration in BALF was detected by the immune turbidimetry. The pathological changes of lung tissues were observed by optical microscope and electron microscope.④Statistical analysis was performed by using SPSS 13.0 statistics software. Results:①The rats became apneic immediately after injury and the breath restored initiatively in a few seconds to a few minutes, then followed by shortness of breath, full-body convulsions, hemiplegia and coma. Some rats occurred dyspnea, cyanosis at oral lips and limbs, meanwhile, there were some haematodes secretions in their mouth and nasal cavity.②The histological changes of the brain tissues and HE staining showed the signs of the cerebral contusion and laceration, cerebral hemorrhage and edema.③From the histological changes of the lung tissues, group B and C presented various degrees of hyperemia, edema and focal hemorrhage, it showed various degrees of micrangium congestion, alveolar septum widened, hydrops accumulation in alveolar space, infiltration of inflammatory cell in interstitial tissue and airspaces by optical microscope. The lung tissues of group B and C showed different levels of pulmonary capillary endothelial cell and mitochondria swelling, villi disappearing, lamellar body emptying by electron microscope.④The levels of NE. IL-8, albumin and water content of the lung tissues from group B increased significantly more than group A (P<0.01). The levels of NE in plasma and BALF, IL-8 in BALF from group C decreased significantly compared with group B (P<0.01), but it was still higher than that of group A(P<0.01). The levels of NE mRNA, albumin and water content of the lung tissues from group C decreased significantly compared with group B (P<.01).but it wasn’t statistically significant compared with the group A(P>0.05). Conclusion:①NE and IL-8 are the important inflammatory factor of lung injury caused by severe brain injury.②It is positively effective to abate lung injury by aerosol inhalation of sivelestat sodium after severe brain injury.③The protection of sivelestat sodium to the severe brain injury with secondary lung injury may be implemented by inhibition of NE activity and reduction of secretion about NE and IL-8.