| Objective:To study the protective effect on newborn rats with hyperoxia-induced lung injury and explore its potential mechanism.Method: 50 newborn rats were divided into control and experimental groups randomly(n=25), to prepare newborn rat models of lung injury in prolonged high concentration of oxygen. The experimental group were injected with caffeine(the first dose, 20 mg/kg; maintenance dose, 5 mg/kg/d), while the control group were provided with the same amount of saline. Five newborn rats would be chosen from each group randomly after 1, 3, 5, 7, 14 day. Then we opened their chest immediately once they were anesthetized with 10% chloral hydrate, isolated lung tissue, ligated the left main bronchus, injected the right lung with normal saline for alveolar lavage. Part of the left lung will be used for wet and dry weight determination, while rest of the lung tissue were fixed in formalin for pathological tissue sections. Finaly, we determined the lung wet/dry weight ratio, took the lung routine pathologic examination, kept radieal alveolar counts(RAC), and applied special stainings on the lung collagen. ELISA method will be used to assay the levels of IL-1?, IL-6, IL-8, IL-10 and TNF-? in the lavage fluid.Results:1. Comparing the control group with the experimental group, the newborn rats lung tissue wet weight / dry weight ratio was lower to the latter. Differences between the two groups had statistical significance(P <0.05).2. Compared with the control group, the content of IC(inflammatory cytokines) in the lavage fluid of the experimental group were lower, such as TNF-?, IL-1?, IL-6 and IL-8, but the level of anti-inflammatory cytokine IL-10 elevated. On the 7th and 14 th day, the differences between the two groups had statistical significance(P <0.05).3. With the extension of time under hyperoxia, the newborn mice in the control group appeared pathological characteristics, which are similar to typical pathology of BPD(bronchopulmonary dysplasia), such as alveoli volume increasing, structure simplifing, alveolar-septal thickening, and RAC obviously reducing. However, after application of caffeine, the lung injury was reduced, and disorder of the lung tissue structure was also improved significantly. Meanwhile, RAC of the experimental group markedly increased. On the 7th and 14 th day, the differences between the two groups had statistical significance(P <0.05).4. On the 14 th day of the experiment, the lung tissue collagen specific staining on pulmonary interstitium demonstrated blue collagen deposition for the control group newborn rats, pulmonary interstitial collagen deposition no however, after applying caffeine the experimental group showed no the case.Conclusion: With extension of time, neonatal rats of the control group had different degrees of acute or chronic lung injury, the content of IC in the lavage fluid were rising, but the level of anti-inflammatory cytokine declined gradually, and the RAC also correspondingly decreased. Eventually, all of these phenomena leaded to pulmonary fibrosis, and occurred the pathological features of BPD. Compared with the control group, the application of caffeine for the experimental group made the level of IC in the lavage fluid decreased significantly, but both the anti-inflammatory cytokines and RAC increased, and the rats didn't appear pulmonary fibrosis, thus reducing the hyperoxia-induced lung injury and preventing BPD. |
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