Experimental Study On The Mechamism Of Pulmonary Fibrosis Caused By Acute Paraquat Poisoning To Injury Of Lungs.

Background:PQ,The trade mame internal is "Ke Wu Zong".The case fatality rate caused by poisoning is very high.The abroad report was 40-50%,and the apart report internal reached above 80%.when PQ enter humanbody,it can caused damages of lungs kidney liver and adrenal gland,and the mark change of poisoning is lung jnjury .It shows the early damage of alveolar epithelial cell,the hemorrhage and the inflammatory cell infiltration.It shows inside pulmonary alveoli and pulmonary interstitial fibrosis.That was named "PQ lung",it is variation style of ARDS ,and it is the main cause of death of PQ poisioning patient.But recent years,the study about mechanism of pulmonary fibrosis have got many important progress.Especially the effect of many intrapulmonic cell and cytokine was noticeable in the complex process.And then it raised the concept of pneumocyte and cytokine network.All kinds of cytokine which were composited by pulmonary alveolar macrophage ,and their type,effect density,high expressed time difference and activation level of its corresponding receptor which were most important during the alveolar epithelium recovery or pulmonary fibrosis.Purpose:1. Apporaching the PQ poisiong mechanism of action. 2.Observing at the acute reaction process caused by PQ poisioning,cytokine which shows its variation regularity. 3.Keeping on tracking the regularity of cytokine TGF -βmRNA ,and approaching the molecular level mechanism of PQ poisioning.4.Observing the regularity of PQ poisoning pulmonary fibrosis throw the patholvgical section and electron microscope checking.Method:1. The preparation of animal model of PQ poisioning:All 24 healthy adult Wister rats were randomizedly assigned into normal control groups, 3days group,7days group and 21 days group.It's poisoning dose is 60 mg/kg. It was divided 3 observing segments of 3d,7d,21d and the standards of TGF-βmRNA and cytokine TGF-β1 were determined.2. Main regent and drug;20%PQ solution:PCR sample storage liquid;and the PCR kit;PDGF,IGF-1,TGF-β1kit.3. Observing index:The detection of lung tissue RT-PCR,serum cytokine PDGF,IGF-1,TGF-β.The check of lung tissue pathology.Result:Cytokine TGF-β1 of the serum was higher in the 3day group than in the NS group (p< 0.01) ,it was descended in the 7 and 21day group but it was still high .Compared to the NS group ,it was higher (P<0.05 ) .PCR TGF-β1mRNA of the lung tissue was higher in the 3day and 7day group than in the NS group(P<0.05) .IT was higher in the 21day group than in the NS group . The pathology discovered that seven days later ,the efflusion in alveolar space begin to organize,fiber-cell overgrowth and it excrete tenuity collaren fiber ,and we can see the picture .because of the ingury of the alveolar epithelium ,the ingury of the II type cell,that we can see the lack of SAM and it appears pulmonary alveoli collapse,the above pathological changes became obviously after 2 weeks later and then develop in progress.Conclusion:During the process of pulmonary fibrosis caused by PQ poisioning,there is regularity changes of TGF-β1,Serum cytokine TGF-β1 was obviously heighten,and it maintained higher level .But the lung tissue TGF-β1mRNA express was obviously increase during 3 and 7-days group,and appeared descended during 21days-group.It was in line with the poisioning course of disease.It illustrated that the cytokine TGF-β1 maybe reach important effect during the course of PQ poisioning and it's detailed mechanism is waiting for more approaching. Background:PQ,The trade mame internal is "Ke Wu Zong".The case fatality rate caused by poisoning is very high.The abroad report was 40-50%,and the apart report internal reached above 80%. when PQ enter humanbody,it can caused damages of lungs kidney liver and adrenal gland,and the mark change of poisoning is lung jnjury .It shows the early damage of alveolar epithelial cell,the hemorrhage and the inflammatory cell infiltration.It shows inside pulmonary alveoli and pulmonary interstitial fibrosis.That was named "PQ lung",it is variation style of ARDS ,and it is the main cause of death of PQ poisioning patient.But recent years,the study about mechanism of pulmonary fibrosis have got many important progress.Especially the effect of many intrapulmonic cell and cytokine was noticeable in the complex process.And then it raised the concept of pneumocyte and cytokine network. All kinds of cytokine which were composited by pulmonary alveolar macrophage ,and their type,effect density,high expressed time difference and activation level of its corresponding receptor which were most important during the alveolar epithelium recovery or pulmonary fibrosis.Purpose:1. Apporaching the PQ poisiong mechanism of action .2.Observing at the acute reaction process caused by PQ poisioning,cytokine which shows its variation regularity. 3.0bserving the regularity of PQ poisoning pulmonary fibrosis throw the patholvgical section and electron microscope checking.Method:1. The preparation of animal model of PQ poisioning:All 72 healthy adult Wister rats were randomizedly assigned into normal control groups,paraquat high dose group (120mg/kg), paraquat middle dose (60mg/kg) group , paraquat low dose group (30mg/kg) .It was divided 3 observing segments of 8h,24h,72h and the standards of TGF-β1,PDGF,IGF-1 were determined.2.Main regent and drug;20%PQ solution:PCR sample storage liquid;and the PCR kit;PDGF,IGF-1,TGF-β1kit.3.Observing index:The detection of lung tissue RT-PCR,serum cytokine PDGF,IGF-1,TGF-β.The check of lung tissue pathology.Result:Every index of the PQ group was significantly higher than that in the NS group at the same section (P<0.05 or P<0.01) .The comparison in the 72h group ,the high dose group was significantly higher than the middle and low dose group (P<0.05 ), and there is no significantly difference between the middle and low dose group.The comparison of index in the same dose group,the group of 72h was much higher than 8h group and 24h group (P<0.05 ) , and there is no more difference between the 8h group and 24h group. The pathology discovered that it was appear broaden and congestive 8h later .and it was more obviously 24h later .We can also see the sign of fibrotic 72h later ,and we saw the appearance of widespread interstitial fibrosis.Conclusion:.During the discovery of research,the level of cytokine was increase gradually with poisoning density increasing,it appears dynamatic changes . The Influence of cytokine PDGF,IGF-1,TGF-β1 during the mechanism of ALI caused by PQ poisioning.