Abstract
Objective To investigate the effect of Rhubarb on bronchopulmonary dysplasia(BPD) and its potential mechanism. Methods Neonatal Sprague-Dawley rats (postnatal day 4) were exposed to 600 mL/L O2 to induce BPD.The experimental rats were randomly divided into 4 groups with 16 in each group: air+ saline group, air+ Rhubarb(600 mg/kg)group, and hyperoxia+ saline group, and hyperoxia+ Rhubarb group.The rats were sacrificed and lung tissues were obtained on day 14 and 21 after birth.Hematoxylin-easin staining was used to detect the pathomorphology of the lungs.Apoptosis of the lung tissue was detected by means of TdT-mediated dUTP nick-end labeling(TUNEL). The expression of Fas was detected by adopting Western blot.The activity of Caspase-8 and Caspase-3 was detected by using spectrophotometer. Results The lung structure of rats was markedly abnormal (decreased, enlarged and simplified alveoli) after being exposed to hyperoxia at any time point.The apoptosis indexes (39.91±1.91 vs.10.11±1.64, 48.80±4.51 vs.12.90±3.18), the expression levels of Fas (0.47±0.02 vs.0.21±0.01, 0.55±0.02 vs.0.22±0.01) and the activities of Caspase-8 (52.59±1.23 vs.40.74±1.08, 60.20±3.48 vs.40.39±2.47) and Caspsase 3 (57.17±1.88 vs.42.00±1.19, 64.57±2.79 vs.41.54±1.27) were all increased in the hyperoxia+ saline group compared with those in the air+ saline group on day 14 and 21, and the differences were statistically significant(all P<0.001). However, compared with the hyperoxia+ saline group, Rhubarb administration dramatically decreased pulmonary apoptosis index (26.49±2.65 vs.22.97±3.66), Fas protein level (0.27±0.03 vs.0.31±0.01) and the activity of Caspase-8 (32.70±2.69 vs.30.66±4.48) and Caspase-3 (44.94±1.60 vs.44.59±1.66), and the differences were statistically significant(all P<0.001). Meanwhile, lung damage after hyperoxia was significantly attenuated in the hyperoxia+ Rhubarb group. Conclusion Rhubarb can reduce the hyperoxic lung injury of BPD by reducing the apoptosis of newborn rat lung tissue cells, and the mechanism may involve the apoptosis pathway of Fas. Key words: Bronchopulmonary dysplasia; Rhubarb; Apoptosis
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