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Transforming Growth Factor Tgf-¦Â <sub> 1 </ Sub> On The Transplant Lung Ischemia - Reperfusion Injury In Rats

Posted on:2005-08-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:T WangFull Text:PDF
GTID:1114360152498224Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective : To investigate endogenous transforming growth factor β1 (TGF- β1 ) gene expression in lung following ischemia-reperfusion in canine, and the role of it in internal organ injury induced by ischemia-reperfusion.Methods: Model was achieved by placing a clip across the left lung phylum. The healthy local canines as experimental were divided into 5 groups, including: Normal control group (sham-operation n=4), ischemia group (ischemia for 45min n=4), reperfusion4h, 12h, 24h group(n=4). Expression of TGF- β1 gene (including mRNA and protein) was observed by Immunohistochemical and reverse transcription polymerase chain reaction (RT-PCR).Results: TGF- β1 mRNA and protein were expressed in normal and injured lung, mainly in alveolar cells, endothelial cells of vein. TGF- 3 imRNA and protein level increased at 45 minutes after ischemia than normal control (P<0.05). TGF- β1 gene expression markedly increased at 4 hours and 12 hours after reperfusion compared with normal control (P<0.05). It returned to normal level after 24 hours reperfusion.Conclusions 1. The results suggest that gene expression of endogenous transforming growth factor- β1 (both mRNA and protein) appears to be up following the time of injure after ischemia-reperfusion in canine lung, and reflects damagesdegree in early inflammation procedure. 2. Endogenous transforming growth factor-β1 way play an important role both in early inflammation procedure and in later lung selfrepair after ischemia-reperfusion insults and protects lung ischemia-reperfusion injury in canines. 3. Applying exogenous transforming growth factor- β1 or improve contents of endogenous transforming growth factor- β1 through gene-transferred technology in early ischemic-reperfusion process may decrease ischemia-reperfusion injury, protect lung allograft, increase succeeding rate in lung transplantation.Objective: To establish an experimental animal lung transplantation model by borrowing clinical lung transplantation, to study the preventive effects and the mechanisms of TGF- β1 (transforming growth factor- β1) in the process of ischemical reperfusion injury in donors in dog. We hypothesize that TGF- β1 attenuate ischemical reperfusion injury and inhibits apoptosis of lung tissue cells.Methods: The healthy local canine were employed as animals for model of lung transplantation. They were divided into 4 groups: Nomal health control (n=4);Saline perfusion (n=4) 45 minutes ; Euro-collins liquor (n=4) perfusion 45 minutes; Euro-collins liquor and TGF- β1 protein perfusion 45 minutes; Lung tissues were procured 4 hours after transplantation and analyzed by RT-PCR (reverse transcriptase-polymerase chain reaction) for bcl-2 mRNA expression. Immunohistochemical for bcl-2 protein., ELISA for TNF-a. HE stine for observing changes of pathologic.Results: Through RT-PCR, we found that bcl-2 mRNA decreased (1.16 + 0.11vs0.85 + 0.73) in group of Saline perfusion , but no significant, bcl-2 mRNA in group of Euro-collins liquor perfusion almost closed to normal, whereas by ELISA TNF-a significantly increased (267.34+47.08 vs 677.5±86.14) in group of Saline...
Keywords/Search Tags:lung transplantation, ischemical reperfusion injury, TGF- β1 (transforming growth factor- β1 ), tumor necrosis factor(TNF- a), apoptosis, Bcl-2, Lung ischemia-reperfusion injury, Immunohistochemical
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