| Objective: To explore the effects of edaravone?EDA? on oxidative stress and alveolar epithelial cell apoptosis in rats model of COPD.Methods: All of the rats were diveded into COPD group, Control group, and edaravone group?EDA group? randomly, every group has 10 rats. 200ug/200 ul LPS was used to intratracheal injection at day 1 and day 14 in the COPD group, then, put COPD group rats in the cigarette smoke box twice a day on day 2 to day 13?day 15 to day 28 to set up COPD rats model. Edaravone group?EDA group?:Use the same method to set up COPD rats model, the difference is that EDA group was intraperitoneal injected Edaravone at a dose of 20mg/kg before exposure to cigarette smoke. Control group: Not to smoke, replace the intratracheal instillation and intraperitoneal injection of drugs with saline. After the last exposure to cigarette smoke, to kill all the rats, The leukocytes and cell sorting of the bronchoalveolar lavage fluid?BALF? was calculated, WST-1 was used to detect the plasma level of SOD of all rats, and TBA was used to detect the plasma level of MDA of all rats. Lung pathological changes were observed by Hematoxylin Eosin? HE? staining, Mean alveolar numbers and Mean linear intercept was measured. Immunohistoehemical was used to analyze the protein expression level of CHOP and Caspase-12, TUNEL was used to detect alveolar epithelial cell apoptosis.Results:?1?General condition: COPD group ratsshowed loss of appetite, weight loss, reduced activity, dark coat color, breathing hard. lips and limbs cyanosis. The rats appeared a significant wheezing, driving response slow and some rats drowsiness, irritability When exposed to cigarette smoke. Rats in control group were in good spirit with good appetite, weight increasing, rosy lips and limbs and moving freely. While the general condition of rats in EDA group was good than COPD group, but worse than the Control group.?2?Total cell counts and neutrophil proportion in bronchoalveolar lavage fluid?BALF? of COPD group?4.54 ± 0.11×108/L, 20.39 ± 2.34%? were higher than Control group?1.53 ± 0.08×108/L, 4.95 ± 0.83%??p?0.05?. After treatment with edaravone, the Total white cell counts and neutrophil proportion in bronchoalveolar lavage fluid?BALF? was lower in EDA group?2.55 ±0.18×108/L, 10.6 ± 2.42%? than COPD group?p?0.05?.?3?In contrast with control group?4.38 ± 0.63 nmol/L?, the plasma MDA in COPD group?8.14 ±0.79 nmol/L? was obviously higher, but the plasma SOD in COPD group?14.94± 2.25 U/ml? was lower than control group?24.54 ± 1.08 U/ml??p<0.05?; After treatment with edaravone, the plasma level of MDA and SOD in EDA group was?5.67 ± 0.82 nmol/L,19.66 ± 1.68 U/ml? respectively,plasma MDA level decreased obviously, but plasma SOD level increased than COPD group?p<0.05?.?4?Hematoxylin Eosin? HE? staining was observed in lung tissue, Compared with the control group, Lung tissue sections of the COPD group showed many inflammatory cells infiltration in the lung tissue and airway, and alveolar structural damage and so on. After treatment with edaravone, inflammatory in the lung tissue and airway, changed for the better. lung tissuemorphological analysis: MLI and MAN of the COPD group were(81.99 ± 6.39 ×10-6m, 89.523 ± 6.99×106/m2) respectively, which of the Control group were(46.14 ± 2.55×10-6m, 161.99 ± 7.86×106/m2) respectively. It showed that MAN of the COPD group decreased obviously, while MLI increased?p<0.05?. After treatment with edaravone, in contrast with COPD group MLI of the EDA group(63.01 ± 4.85×10-6m) decreased obviously, and MAN of the EDA group?112.85 ± 9.36×106/m2? increased obviously?p<0.05?.?5?The result of immunohistochemistry showed that Caspase-12 and CHOP mainly expressed in alveolar epithelial cells. IODs of Caspase-12 and CHOP in the COPD group were?10150.9 ± 273.9, 9884.1 ± 265.9? respectively, which is obviously higher than the Control group?1456.9 ± 87.5, 1072.4 ± 136.2??p<0.01?. In contrast with COPD group, the IOD of EDA group?6443.9 ± 312.4, 6128.9 ±195.4? was obviously lower than COPD group?P<0.05?.?6?TUNEL was used to detect alveolar epithelial cell apoptosis. The AI of COPD group?40.61 ±1.86%? were higher than the Control group?10.4 ± 1.17%??P<0.01?.In contrast with COPD group, the AI of EDA group?24.75 ± 1.71%? decreased significantly?P<0.05?.Conclusion: Edaravone attenuates alleviating oxidative stress, ERS and alveolar epithelial apoptosis in COPD rats, which may be associated with antioxidant effect of Edaravone. |
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