The Influences Of Interfering With Plasma Hydrogen Sulfide Levels On Pulmonary Vascular Permeability Of Septic ARDS

Objective:1 To observe the relationship between plasma hydrogen sulfide and pulmonary vascular permeability of septic ARDS and the effect of changing plasma hydrogen sulfide with sodium hydrosulfide on pulmonary vascular permeability of septic ARDS.2 UTI which can affect gas signaling molecule nitric oxide and carbon monoxide was used on rats with septic ARDS to observe the changes of gas signaling molecule hydrogen sulfide and determine whether UTI can regulate plasma hydrogen sulfide.Then the anti-inflammatory mechanism of ulinastatin was talked.By completing the above two aims whether we could use UTI to change the plasma hydrogen sulfide levels to influence the pulmonary vascular permeability of septic ARDS and alter the pathophysiology of ARDS was determined.The mechanism of clinical anti-inflammatory drugs ulinastatin was determined and a thought for the future pharmaceutical research ARDS was provided.Method:80 healthy male SD rats,according to the random number table,were completely randomized divided as control group,septic ARDS group,sodium hydrosulfide group and ulinastatin group,20 rats in each group.（1）Control group: laparotomy,but not for the ligation and perforation of the appendix,16 hours later the blood gas analysis and intraperitoneal injection of normal saline 1ml were operated.（2）Septic ARDS group : the model of acute respiratory distress syndrome was induced by cecal ligation and puncture（CLP）,the blood gas analysis and intraperitoneal injection of normal saline 1ml were performed 16 hours later.（3）Sodium hydrosulfide group: Cecal ligation and puncture,16 hours later blood gas analysis and intraperitoneal injection of sodium hydrosulfide（according to 28umol/Kg into 1ml liquid）was performed.（4）Ulinastatin group: Cecal ligation and puncture,16 hours later blood gas analysis and ulinastatin according to the 10 million units /Kg were given with 1ml solution,via the femoral vein injection.We regard respiratory distress,cyanosis,lung smell and wheezing in singing,refractory hypoxia status was not spontaneous remission to ARDS Pa O2/Fi O2≤ 300 as the standard of success model.48 hours later,blood gas analysis,plasma hydrogen sulfide（H₂S）,bronchoalveolar lavage fluid protein,lung tissue of evans blue content and wet-to-dry weight were detected.At the same time lung tissue pathology were observed with optical microscopy and electron microscopy.SPSS13.0 statistical software was used for analysis.The different indicators of different groups were compared.ANOVA was used to compare the indicators among more than two groups.The indicators between two groups were compared with q test.Plasma hydrogen sulfide in the septic ARDS group and vascular permeability index were conducted by correlation analysis with pearson method.We regard P<0.05 as the difference has statistical significance.Result:1 Blood gas analysis:The mean value of arterial oxygen partial pressure in the septic ARDS group was lower than that in the control group.PaO2 in the sodium hydrosulfide group and ulinastatin group were lower than the control group,but higher than the septic ARDS group.2 Plasma hydrogen sulfide concentration:Compared with control group,the plasma hydrogen sulfide concentration in the septic ARDS group was significantly decreased.Compared with the septic ARDS group,the plasma hydrogen sulfide levels of sodium hydrosulfide and ulinastatin group were significantly increased,but still lower than the control group.3 Alveolar lavage fluid protein concentration:Compared with control group,the alveolar lavage fluid protein concentration in septic ARDS group was increased.Compared with the septic ARDS group,the alveolar lavage fluid protein concentration in sodium hydrosulfide group and ulinastatin group was decreased.4 The content of evans blue:Compared with the control group,the evans blue content was significantly increased in the septic ARDS group.Compared with the septic ARDS group,the leakage of evans blue content in sodium hydrosulfide group and ulinastatin group was decreased.5 Wet-to-dry weight ratio comparison:Compared with the control group,the lung wet-to-dry weight ratio was significantly increased in the septic ARDS group.Compared with the the septic ARDS group,the lung wet-to-dry weight ratio of sodium hydrosulfide and ulinastatin group were decreased,but higher than that in the control group.6 Optical microscopy observation: In control group,the alveolar structure was clear,and there was no inflammatory cell infiltration in the alveolar and interstitial.In the septic ARDS group,the alveolar cavity became narrow,the alveolar wall was obviously thickened,pulmonary interstitial edema,alveolar edema fluid was obviously found.Compared with the septic ARDS group,the injury of sodium hydrosulfide and ulinastatin group was reduced.7 Electron microscope observation:Control group,the vascular endothelial cell nuclear and cytoplasmic was clear,mitochondria and rough endoplasmic reticulum was normal,tight junction was not open.The ultrastructure of lung tissue in septic ARDS group was significantly impaired,endothelial cell cytoplasm and cell nuclear was degeneration and necrosis,we can only see the contour.Compared with septic ARDS group,the injury of lung ultrastructure in the sodium hydrosulfide group was reduced,endothelial cells was normal,mitochondria was slightly swollen.Compared with septic ARDS group,the injury of lung ultrastructure in the ulinastatin group was reduced and endothelial structure was basically normal,a small part of the cell membrane and cristae were blurred.8 Correlation analysis:（1）The level of plasma hydrogen sulfide in septic ARDS group was negatively correlated with the lung wet-to-dry weight ratio（r=-0.835,P<0.05）.（2）The level of plasma hydrogen sulfide in septic ARDS group was negatively correlated with alveolar lavage fluid protein（r=-0.817,P<0.05）.（3）The level of plasma hydrogen sulfide in septic ARDS group was negatively correlated with the content of evans blue in the lung tissue（r=-0.854,P<0.05）.Conclusion:1 Hydrogen sulfide can regulate pulmonary vascular permeability of septic ARDS and the decline of Hydrogen sulfide can lead to the vascular permeability increase.Exogenous hydrogen sulfide can improve pulmonary vascular permeability of septic ARDS.2 UTI has many anti-inflammatory mechanisms which also can change the level of H₂S to affect ARDS pulmonary vascular permeability.