The Protective Effects Of Xuebijing Injection On Hyperoxia-induced Lung Injury In Neonatal Rats

Background Numerous studies have confirmed that prolonged inhalation of high concentrations of oxygen not only can cause acute lung tissue damage, but also can affect the further development of neonatal lung tissue, leading to bronchopulmonary dysplasia (BPD) of the occurrence and prognosis of severely affected newborns quality of life, and the treatment of hyperoxia-induced lung injury is still no effective method. Xuebijing injection from safflower, Chuanxiong, Salvia, Angelica, Paeonia, composed of pure Chinese medicine, used for sepsis, multiple organ dysfunction syndrome (MODS) in the treatment, and obtained significant effects.Objective By observing the protective effects of Xuebijing injection on hyperoxia-induced lung injury in neonatal rats.Methods The 22-day gestation full term rats in 12 hours after birth were randomly marked with a different number and assigned to six groups:air+NS group (AN group),air+Dexamethasone group (AD group), air+ Xuebijing group (AX group), group,hyperoxia+NS group(HN group), hyperoxia+ Dexamethasone group(HD group) and hyperoxia+ Xuebijing group (HX group). Observing the Effects of high oxygen on the general situation of newborn rats and mortality. The ratio of lung wet weight to lung dry weight (wet-to-dry weight ratio,W/D), the content of protein,LDH, TNF-αand IL-10 of bronchoalveolar lavage fluid (BALF), the counts of inflammatory cell in BALF,and lung tissue HE staining, of hyperoxia-induced lung injury were measured respectively.Results 1. Case fatality ratio:With the extension of time of hyperoxia exposing, the animal case fatality ratio increases. Xuebijing can obviously lower the case fatality ratio of neonatal rats which were exposed in hyperoxia environment for 5 days and 7 days (P<0.05). 2.Leucocyte Counts in BALF:All the Leucocyte counts in HN Group is higher than AN group in the same time point (P<0.01). Dexamethasone can ease the abnormal Leucocyte counts raise of hyperoxia group in the 3-day and 5-day exposing (P<0.01). Xuebijing can significantly lower the Leucocyte counts in BALF in 5-day and 7-day group (P<0.01 without exception).3. LDH and Protein content in BALF:The LDH and Protein content in BALF of hyperoxia group are high than the AN group in the same time point (P<0.05 without exception). Both Dexamethasone and Xuebijing can lower the increase of LDH and Protein content in BALF of after 5-day and 7-day exposing (P<0.05 without exception). And, with the longer experimental time, the effect of Xuebijing is more obvious than the effect of Dexamethasone (P<0.01) 4.TNF-a in BALF: Compared with Air-physiological Saline Group, the TNF-a content in BALF of HN Group and HD Group significantly increased (P<0.01 without exception). The TNF-αcontent in BALF of Hyperoxia Group which have given Dexamethasone and Xuebijing, has significantly decreased (P<0.01 without exception), and HX Group decreased more obviously (p<0.01).5. IL-10 Content in BALF:Compared with AN Group, the IL-10 content in Hyperoxia Group significantly lowered (P<0.01 without exception). Compare Hyperoxia Group which have given Dexamethasone and Xuebijing to HN Group, IL-10 in BALF significantly increased (P<0.01 without exception), and the HX Group increased more obviously (P<0.01).6. W/D Ratio:After exposing for 5 days and 7 days, HN Group is significantly higher than AN Group and AD Group (P<0.01 without exception). Dexamethone can only lower the increased W/D Ratio after hyperoxia exposing for 7 days. After hyperoxia exposing for 5 or 7 days, HX Group is significantly lower than HN Group (P<0.01 without exception).7. Lung tissue HE staining: Having 3 days exposured to hyperxia, structure of lung tissue is disorder, interstitial edema, a large number of red blood cells and inflammatory cells can be seen in alveolar; continued high exposure to 5 days and 7 days of oxygen, a more disordered structure of the lung tissue, lung interval widened, and pulmonary stromal cells increased. HX group can reduce the inflammatory exudates in lung tissue and improve the organizational structure of the lung disorder.8. Radial alveolar count (RAC):RAC of normal neonatal rats lung tissue, gradually increased the value after birth, in 5 days,7 days were obviously higher than the previous point in time(P all<0 05). Sustained high oxygen exposure in the lung tissue 3 days, the RAC value was no significant difference with the air group, with the extended high-oxygen exposure,significantly inhibited the increase in the value of RAC,until 7 days after birth was significantly lower than the air control group(P<0 01). Xuebijing can increase the RAC values of Hyperoxia group at the same time point. (P <0 05)Conclusion 1.Successfully established the model of hyperoxia-induced lung injury in neonatal rats.2.hyperoxia exposing in neonatal rats can cause pulmonary proinflammatory and anti-inflammatory factor of the imbalance, causing acute lung injury, and inhibite the normal development of the lung after birth.3.Apply dexamethasone when hyperoxia exposing can improve pro-inflammatory and anti-inflammatory factor of the imbalance, reduce the degree of acute lung injury induced by hyperoxia, but can further inhibite the development of lung which injured by hyperoxia after birth.4.Compare with dexamethasone,apply xuebijing when hyperoxia exposing can better improve pro-inflammatory and anti-inflammatory factor of the imbalance, reduce the degree of acute lung injury induced by hyperoxia efficiently,and do not inhibite the development of lung which injured by hyperoxia after birth.