| Objective: To investigate the relationship between the changes of the level of endothelin-1(ET-1)and the inflammatory response and the injury of liver and kidney,to provide experimental data for further research.Methods: 72 healthy and clean male Sprague-Dawley rats,weighing 250-350 g,randomly assigned into two groups,a control group(Group A,36): without intracranial compression,other operations were the same as the brain death group;a brain-dead group(Group B,36): a codman intracranial pressure probe and a 3F Fogarty balloon catheter were placed intracranially,according to the relationship between intracranial pressure and mean arterial pressure,the stable brain death models were established by progressive and increasing intracranial pressure with water injected at a rate of 16 ?L/min into fogarty balloon catheter,and through the respiration and circulation to maintain brain death status 6 h.Determine the standard of brain death which as the following criteria:(1)No spontaneous breathing;(2)Corectasis and light reflection disappeared;(3)Absent corneal reflex;(4)Electroencephalogram resting potential.The blood samples were collected from the femoral artery at the following time points: the time after the routine surgical operations were accomplished and before ICP was increased(T1),the time that the experimental animal met the brain death criterion(T2),and at 1(T3),2(T4),4(T5)and6(T6)hours after brain death.Inflammatory mediators(ET-1,TNF-?,IL-1?,IL-6 and IL-10)and organ biochemistry markers(ALT,AST,SCr and BUN)were measured and analyzed.HE stain was performed to observe the changes of hepatic and nephric histomorphology.Measurement data was analyzed by SPSS 20.0 Statistical Analysis Software and considered to be normally distributed and expressed as mean ± standard deviation(±s)Statistical comparisons among groups were performed by Student's t-test and correlation analysis used Pearson correlation analysis.The difference was considered to be significant at P<0.05.Results:(1)B group: all of 36 rats were successfully established stable brain-dead model and success rate of 100%,and the model could be maintained 6.17±0.34 h byeffective respiration and circulation.(2)Changes of inflammatory mediators: the levels of ET-1 in serum increased significantly at the time of brain death and the levels of TNF-?,IL-1?,IL-6 and IL-10 were significantly increased from 2 h after brain death in the brain death group,and the above indexes gradually increased with the time of brain death went by.(3)Changes of organ biochemistry markers: The levels of serum biochemical markers(ALT,AST,SCr and BUN)increased significantly from the time of 4 h after brain death and increased gradually with the time went by.Conclusion:(1)Under monitoring the real-time intracranial pressure,applicating continuous improvement of intracranial pressure method can establish stable rat brain death model that could be maintained 6 h by effective respiration and circulation.The model was simple,repeatable and highly successful.The vital signs were relatively stable both at the time of intracranial compression and brain death state,which provided a solid foundation for the further study of the correlation between endothelin-1 and inflammatory response and organ injury.(2)Brain death could increase the levels of ET-1,TNF-?,IL-1?,IL-6 and IL-10 which increased gradually with the prolonged duration of brain death,and ET-1 increasd earlier than other inflammatory mediators and ET-1 was positively correlated with other inflammatory mediators,which speculated that brain death could lead to the increase of ET-1 that leaded to the synthesis and release of inflammatory mediators and then stimulated the acute non-specific inflammation.(3)The levels of ALT,AST,SCr and BUN were increased significantly from the time 4 h after brain death and increased gradually with the prolonged duration of brain death,and inflammatory mediators increased significantly earlier than the biochemical indexes,the biochemical index was positively correlated with ET-1,which suggested that the acute nonspecific inflammation caused by ET-1 was one of the mechanisms of organ damage,and ischemia and hypoxia of tissues and organs caused by ET-1 damaged the organ further. |
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