| ObjectiveLung transplantation has been considered as the only effective treatment for the end-stage lung diseases.Since1963,Doctor James Hardy of the University of Mississippi had carried out the first lung transplantation on human in the world till the end of2009,worldwide lung transplantation was done about32652cases. Although the successful rate of lung transplantation has increased each year,the total of lung transplantions has not met to the corresponding promotion.Donor shortage restricted the development of lung transplantion.In recent years,with the lung transplantion needs increase,the shortage problem of donor lung is becoming serious.At present,in most countries and regions the brain dead donor was transplant surgery as the major source of the transplantion lungs.Brain dead donor has become the main way to solve the donor shortage.However,brain death is a very complicated pathological physiology process.The influence of the brain death on the other parts of body is aa irreversible serious damage of multi-organs.Yet the mechanism of lung damage following brain death is still not completely clear.In the process of brain death,the body's physiological and pathology changes are mainly hemodynamic changes,inflammation,the endocrine disorder,etc.These were found in the animal experiment and clinical study.Among of which, the occurrence of inflammatory response in the organ damage is one of the important factors.Many researches showed that the onset of brain death increased secretionsof IL-1β,IL-6and TNF-alpha,led to abnormal immune reactions,and resulted in the damage of donor organs.Since long time ago,hormones have applied as anti-inflammatary medicine to clinical treatments.Glucocorticoid has a powerful anti-inflammatory effect.It can restrain many kinds of inflammations(such as:physical, chemical,infectious,aseptic,etc.).Brain death process belongs to acute inflammation, yet hormone may restrain leucocyte infiltration and devouting response,reduce the release of inflammatory factor to protect the donor organs. This research through analyzing the levels of IL-1β,IL-6and TNF-alpha in seram,the expression of their mRNA and whater content in donor lung histology had evaluated protective effects of glucocorticoid on donor lung from brain death pig following establishment of the pig brain dead animal model.Materials and methods:Banna XiaoEr Pigs:12,weight25±5kg.Randomly divided into two groups,namely brain death in control group(control group,the group C)and brain death hormone treatment group(hormone group,group H),six pigs in each group.Every group is in vein general anesthesia before tracheas cut and the tubes thrusted in, breathing machines help to breathe internal jugular&artery,bladder and colostomy.The slow intracranial pressure increment method was used to establish the brain dead model and maintained10hours.Group C-only was given a Green solution injection.Group H based on this was added with the methylprednisolone sodium succinate(15mg/kg).The two groups of animals'heart rate(RH),mean arterial pressure(MAP) were recorded during the whole experiment; took out vein blood separately,determined IL-1β,IL-6and TNF-alevels during a period of2,4,6,8,10hours before establishing the model of epidural pressure and after confirming brain death.In maintaining brain death after10hours,pulled the animal model's blood,analysed the blood gas; took lower right lung tissue,to analyse IL-1β,IL-6and TNF-a mRNA amount of expression.At the same time,regular pathological analysis for every group was done.SPSS17.0software was used for this experiment data,statistical data mean±standard deviation expression was also used,single factor analysis of variance was used for comparison between the groups as well,and compared in the group,the use of the design of repetitive measure variance analysis,significant inspection standard a=0.05taken.Results:l.The level of IL-1β(3,IL-6,TNF-a in Group C was gradually higher after brain death,and it was significantly difference(p<0.05) compared with Group H after brain death in0h,2h,4h,6h,8h,10h. 2.The changes of IL-Iβ mRNA,IL-6mRNA,TNF-a mRNA:The level of IL-1mRNA,IL-6mRNA,TNF-amRNA in Group C was gradually higher after brain death,and it was significantly difference(p<0.05) compared with Group H after brain death10h in lung tissue.3.Comparison of lung water content in the two groups:It was significantly higher in the Group C than in the Group H.4.Under the light microscopy,C group has a broadened lung edematous, extravasate in the alveolar congestive capillary vessel, compensatory emphysema,infiltration of white blood cell were observed.Under the electron microscopy,cytoplasm edema, swollen mitochondria of the type Ⅱepithelial cells and the type I epithelial cell,partial membrane dissolution of mitochondria were observed, lamellar body exhausted and the microtomentum disappeared.No obvious morphological injury was observed under light microscopy and electron microscopy in Group H.Conclusion:l.By the way of using slow discontinuous increasing intracranial pressure,brain death model of12pigs were successfully established.Although there are2experimental pigs failed to maintain a state of brain death for10hours,this brings us to a state of brain death in the extreme instability awareness,also make we recognize the importance of combined use of vasoactive drugs.Meanwhile,it offer the practical experience and theoretical basis for more producting successful and a longer maintain of brain death model.2.During establishment of brain death model by intracranial injection compression process,12pigs showed brief convulsions.We think that may be a characteristic performance of sharp increases in intracranial pressure,so it can be used as an indicator of brain death.3.Lung water content of Group C was higher than that in the Group H, and C group of lung tissue cell injury was significantly severer as in lung tissue cells of H group,administrion of glucocorticoid can protects on the AEC1,AEC Ⅱ cells.cells of pulmonary vascular endothelial cell structure,from pulmonary edema.Hormone replacement therapy has protective effection basis on our results,brain death donor lung preservation. 4.Glucocorticoids can suppress the gene expression of inflammatory factors to reduce the amount of inflammatory factors after brain death,decrease the excessive immune response,to improve the quality of donor to lung for lung transplantation. |
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