The Change Of The Cell Apoptosis And The Express Of The Fas/FasL In Pulmonary Fibrosis And The Role Of The NAC | | Posted on:2006-04-13 | Degree:Doctor | Type:Dissertation | | Country:China | Candidate:J C Li | Full Text:PDF | | GTID:1104360152996686 | Subject:Internal Medicine | | Abstract/Summary: | PDF Full Text Request | | Interstiltial lung disease (ILD) is a spectrum of disease is constit with many different diseases. There are many similar characters between these disease in clinical symptom, image, lung function and so on. The pathogenesy pathology is similair. The disease region include the alveolar epithelium , vascular endothelial cell and the other essence cell, not only the interstiltial of the lung, and the disease region can involve the bronchiole region beside the alveolar well. The bronchiole region and the alveolar well fibrosis caused the complaisance of the lung degraded the volume of lung decrease and the dysfunction ventilation. On the other hand the inflammation of bronchiolar and block of the lung small vessels cause the disproportion of the ventilation and flow of blood and the disorder of the diffusion function,in turn the hyoxemia and the repiratory failure would occurrence.The thinking about ILD has become deeply since Liebow published the pathology classification of the diffuse fibrotic lung disease in 1968, but the specific pathogenesy still is unknown yet. This condition make the treatment become very difficult. The role of cell apoptosis was noticed more and more by many scholar follow the advancement of the pathology. The cell apoptosis is induced by apoptosis gene in turn the death program that has existed in the cell and the the cell death would take place. This process is contoled by gene. Fas is named Apo -1, CD95, belong to the supper - family of acceptor of TNF /acceptor of growth factor receptors, contain the death domain. There is basal expression in lung normal. The apoptosis would take place when the Fas bonding to the FasL and takeimportant role in many disease. The alveolitis is normal stage in ILD. The oxida-tive stress and flame cell infiltrate are very stronge factor to induce the cell apop-tosis. It can cause the up - regulat of apoptosis gene in turn up - regulat the cell apoptosis and take very important role in the development of the disease.So we detect the change of cell apoptosis and the expression of Fas/FasL gene and protein. To initially investigate the mechanism of the change of Fas / FasL gene and protein and to investigate the role of NAC.1. The change of the leve of Fas/FasL in BALF and serum of patients with IPFObjective: To detect the change and the significant of the level of Fas/FasL in the BALF and the serum of the patients with IPF. Methods: The ELISA was used to detect the level of Fas/FasL and SOD/MDA in serum and BLAF of patient with IPF. HRCT and the lung function was examined. The data was analyzed by statistics. Results:The level of Fas( 141. 23 29. 18) ,FasL(59. 89 13. 69) in BLAF of patients with IPF is high than control ( P <0. 01) .The level of Fas (3.29 1. 75) , FasL(1.76 0.74) in serum of the patients with IPF, compare with the contol group contrast is not significance (P >0. 05). The statistics analytic shows that the Fas/FasL in BALF of the patient with IPF is positive correlation with the HRCT and lung function. The level of SOD (25.45 8.20) in BALF of patient with IPF is lower than control, the level of MDA (26. 96 6. 37) is higher than control(4.51 0.95) the contrast is significant. The level of FasL in BALF of patient with IPF is postitive correlation with the level of MDA, but The level of Fas is not correlation with the SOD and MAD. Conclusion: The level of Fas/FasL in BALF of patient with IPF is increasing and correlation with the red-ox state of lung and take very important role in IPF.2. The change of cell apoptosis and Fas/FasL gene in experiment lung fi-brosisObjective;To detecte the change of the cell apoptosis and Fas/FasL gene and to investigate the significance of cell apoptosis and Fas/FasL gene in IPF. Method: Make the model of the pulmonary interstitial fibrosis induce by bleocin. To kill the animal in 28 day. The TUNNEL , electron microscope , in situ hubrid-ization, immunity was used to detect the level of cell apoptosis, Fas/FasLmRNAand the protein and the SOD/MDA was detected. Result:The index of lung cell apoptosis in experiment group (18. 36 3. 76) is higher than that one in control group (t = 13.5, P < 0.01). The electron microscope shows the cell apoptosis appeared on the pulmonary epithelial cells, vascular endothelial cell. The expression of FasmRNA and FasLmRNA in the rats'lung tissues of experiment group is higher than controls(t = 15.93). The difference is significenc ( P < 0. 01). The expression of Fas/FasL protein in experiment (97. 06 11.78,110.45 15.28) is higher than control group(P <0.01). The level of SOD(71.11 18.68) in experiment group is lower than the level in control but the level of MDA is higher in experiment group than control. , MDA ( 8. 32 1. 47). Conclusion; The index of cell apoptosis in lung with ILD and takes very important role in the occurance and developmemt. The cell apoptosis in ILD is related with the expression of Fas/FasLmRNA and protein, at the same time Fas/FasL gene and the protein is related to the redos state in BALF with ILD. The oxidation stress cause the increasing of the expression of Fas/FasLmRNA and protein, in turn lead to the cell apoptosis upgraduation of the lung tissues , might take very important role in ILD.3. The role of NAC to intervention the expression of Fas/FasL gene in rats lung with ILDObjective:The NAC was used to intervention the rat with ILD,detected the index of cell apoptosis , the change of Fas/FasL gene and to investigate initially the possible mechanism. Method: The NAC was givent to the rat with ILD by BLM by intragastric administration. Theindex of cell apoptosis was detected, Fas/ FasL — mRNA and protein by in situ hubridization, immunity , MDA and SOD in BALF was detected. Result:The index of cell apoptosis in treatment group (8.14 0. 89) was lower than control group(17.82 11.49) ,the difference is significant (t =9.92,P <0.01) ;The expression of FasmRNA( 108.28 ± 11.49)/FasLmR-NA( 117.57 ±7.16) in treatment group is lower than control group(93.08 ± 13. 24,96.86 ±7.78) o The level of SOD in the rat's BALF is higher than that in control group but the level of MDA in treatment is higher than that in control group. Conclusion:NAC can down upregulat the rat' s index of cell apoptosis with ILD. This phenomenon might be related with the NAC antio oxidation lead... | | Keywords/Search Tags: | pulmonary fibrosis, bronchoalveolar lavage fluid, Fas, FasL, superoxide dismutase, malondialdehyde, N - acetyl -1 - cysteine | PDF Full Text Request | Related items |
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