Effects Of Acetylresveratrol On Acute Lung Injury Induced By Perfluoroisobutylene Inhalation In Rats

Background： Acutelunginjury (ALI) is characterized by damage to theendothelial and epithelial cells in lungs, thereby increasing pulmonary vascularpermeability, pulmonary edema, and sequestration of polymorphonuclear neutrophils,which finally impairs respiratory function even death. The true mechanisms whichcaused ALI remain unclear, however, it is generally accepted that ALI is an excessiveuncontrolled inflammatory response mediated by several pro-inflammatory mediators.AcetylResveratrol (ARES),3,5,4’-tri-O-acetylresveratrol, which is a more stableresveratrol prodrug. ARES was slightly more potent than Res and was used in ourresearch to figure out whether it has preventive activity and therapeutic effects in LPSinduced ALI.Objective:1) Establish and determinate the LPS induced ALI model;2) Based on this model, evaluate the potential preventive activity and therapeuticeffects of ARES;3) Investigate the mechanisms of LPS induced ALI and evaluate the potential newtherapeutic strategies.Based on LPS induced ALI model, we presumed the degree of the lung injury, andalso evaluate the preventive activity and therapeutic effects of ARES.Methods: The healthy Wistar rats were obtained from the Experimental AnimalsCenter of Dalian Medical University, which were cultured in wire cages in a roommaintained at22°C with a12h light/dark period to be prepared for the ALI model. Based on the model, our experiment was carried out as follows;1) Establish and determinate LPS induced ALI model to observe the changes of ratlungs in morphology and traits;2) Examination the effects of ARES on morphology of lungs which comparedbetween normal and ALI group by H&E analysis;3) Examination the lung coefficient, total protein content in bronchoalveolar lavagefluid and pulmonary capillary permeability;4) Evaluated the expression of inflammatory cytokines COX-2in pulmonary tissuehomogenate by RT-PCR.5) Statistically calculations of the data were performed using SPSS11.5Software.Differences in measured variables using t-test、One-Way ANOVA and Mamm Whitneyanalysis. P <0.05was considered statistically signifcant.Results:1) Successfully established LPS induced ALI rat model;2) The colour of the exposed lung compared to normal lung is deep red, and theexposed lung shows deeply increased in size, shiny smooth surface, covered withbleeding, also accompanied by large edema fluid seepage;3) The results of H&E showed normal rat lung tissue has visible bronchial andalveolar tissue which has clear and complete structure, the size of alveolar werebasically the same, thin alveolar wall cavity without congestion and edema; howeverseverely damaged alveolar tissue was showed in ALI model, cell wall thickening withstenosis and cloth soaked red dye, and severe alveolar edema with diffuse large numberof red blood oozing, diffuse alveolar atelectasis. Large concentration of neutrophils andmacrophages on alveolar surface; Administration prevention and treatment groupscompared to ALI model group showed the complete alveolar structure, the bubble wallthickening was not significant, a small amount of edema fluid in bubble cavity, lungsurface accumulation of the neutrophils and macrophages which were accumulated onlung surface were less than other group;4) ALI rats group compared to control group had significant differences in wet/drycoefficient (P<0.05). Pulmonary capillary permeability and total protein content inBALF had significant differences (P<0.01);5) Prevention and treatment group compared with ALI lung showed significantdifferences in wet/dry coefficient (P<0.05), total protein content in BALF and lungcapillary permeability were extremely significant differences (P<0.01). 6) RT-PCR results showed that the expression of COX-2in ALI group wassignificantly increased after2h, and the expression of COX-2was significantly higherthan normal group after8h. The expression of COX-2in prevention group was lowerafter2h. After8h, the expression of COX-2was nearly close to normal group. Theexpression of COX-2in treatment group after2h,8h compared with prevention grouphas downgraded, but it is still significantly higher than the normal group.Conclusions: The rats treated by ARES before or after LPS can reduce rat lungprotein acetylation leakage, improve blood barrier permeability, reduce the degree oflung edema, reduce the inflammation in the lung tissue homogenate factor COX-2,which showed prevention and therapeutical effect to ALI in rats.