Protective Effect Of Xuanbai Chengqi Tang On Lung Injury In Mice With Acute Respiratory Distress Syndrome

Objective: Acute respiratory distress syndrome(ARDS)is an acute diffuse lung injury caused by various intra-and extra-pulmonary pathogenic factors,characterized by refractory hypoxemia and respiratory distress,with high clinical lethality and lack of effective drug treatment.In this study,we investigated the effect of Xuan Bai Cheng Qi Decoration on the inflammatory response of lungs in ARDS mice by constructing a mouse model of acute respiratory distress syndrome(ARDS)induced by Lipopolysaccharide and explored the related mechanisms.By comparing the histopathological changes in the lung,total protein exudation of bronchoalveolar lavage fluid,expression of pro-inflammatory factors interleukin 1β and cyclooxygenase 2,and changes in the expression of P38 and phosphorylated P38 proteins,which are key to regulate the inflammatory signaling pathway,we investigated the specific mechanism of the protective effect of Xuan Bai Cheng Qi Decoration on the regulation of P38 MAPK signaling pathway in lung injury and explored the methods for the prevention and treatment of ARDS and the application of its clinical drugs in the future.This study will provide new scientific ideas for future research and development of ARDS prevention and treatment methods and the application of clinical drugs.Method: Eighteen male healthy adults(4-6 weeks old)C57BL mice were selected and randomly divided into 3 groups: control group(Control group),model group(LPS group),and Xuanbai Chengqi Tang treatment group(XCD+LPS group).Xuanbai Chengqi Tang treatment group: Xuanbai Chengqi decoction was composed of rude rhubarb 18 g,bitter almond 12 g,gypsum 30 g,and pericarpium trichosanthis 9 g.The dose of Xuanbai Chengqi decoction was 13.8 grams per kilogram of body weight.Model and Xuanbai Chengqi Decoction treatment groups were given intraperitoneal injections of LPS 15 mg/kg for modeling,whereas the Xuanbai Chengqi Decoction treatment group was given gavage twice daily after modeling.A similar volume of normal saline was administered by gavage to the model group at the same time after modeling.The control group received the same dose of normal saline intraperitoneally to establish the model,and the same volume of normal saline was gavaged at the appropriate time after the model was established.After 24 hours of LPS modeling,the mice were anesthetized and sacrificed.We observed the living behavior,mental status,and external hair of each group of mice;in addition,we stained the pathological sections of lung tissue with hematoxylin and eosin(HE)to observe the histopathological changes of the lung in each group.The alveolar-capillary barrier was damaged and lung inflammation was evaluated by measuring the protein level in bronchoalveolar lavage fluid and IL-1β mRNA expression in lung tissue.The Western blot method was used to determine the changes in protein expression of cox2,p38,and p-p38 in the lung tissues of each group.Results:(1)Mice in the control group were mentally fine,had normal eating and drinking behavior,could quickly avoid and resist when grasping,had dense and lustrous fur,and had no abnormal breathing.mice in the model group were depressed,mostly seen lying still in place,were unable to avoid and resist when grasping,had dull fur,rapid breathing,and occasionally had their limbs curled up and trembling,unable to stand upright.The above symptoms were alleviated in the Xuanbai Chengqi Tang treatment group compared with the model group.(2)Histopathological findings of the lungs showed that inflammatory cell infiltration(mainly neutrophils)and erythrocyte leakage,hyaline membrane formation,and widening of alveolar septum were seen in the alveolar lumen and alveolar septum of the model group compared with the control group,while inflammatory cell infiltration and erythrocyte leakage in the alveolar lumen and alveolar septum of the Xuanbai Chengqi Tang treatment group were reduced compared with the model group,and the widening of the alveolar septum was reduced.(3)The total protein level and the expression level of pro-inflammatory factor IL-1βmRNA in lung tissue in the bronchoalveolar lavage fluid were significantly higher in the model group compared with the control group(P<0.05);the total protein level and the level of pro-inflammatory factor IL-1β mRNA in lung tissue in the Xuanbai Chengqi Tang treatment group were significantly lower compared with the model group(P<0.05).(4)Western-Blot results showed that the expression of the p38 protein was not statistically different in all groups(P>0.05).Compared with the control group,p-p38 and COX2 protein expression were both up-regulated in the model group(P<0.05),and no statistical differences were observed in the p-p38 and COX2 protein levels in the Xuanbai Chengqi Tang treatment group compared with the control group(P>0.05);compared with the model group,the p-p38 and COX2 protein expression levels decreased in the Xuanbai Chengqi Tang treatment group,and the differences were statistically significant(P<0.05).Conclusion: Xuanbai Chengqi Tang can participate in the regulation of the pulmonary inflammatory response in acute respiratory distress syndrome through the p38 MAPK signaling pathway,which can reduce the expression of the inflammatory factor IL-1β mRNA in lung tissue under lipopolysaccharide-induced inflammation,and can reduce the expression of cyclooxygenase 2 protein,thereby reducing the inflammatory response and thus improving the alveolar-capillary barrier function in the lung to play a pulmonary protective role.