| Acute lung injury is the injury of alveolar epithelial cells and capillary endothelial cells caused by various direct and indirect trauma factors,causing diffuse pulmonary interstitial and alveolar edema,resulting in acute hypoxic respiratory insufficiency.Lung volume reduction,reduced lung compliance,ventilation/blood flow imbalance are the pathophysiological characteristics.Clinical manifestations of progressive hypoxemia and respiratory distress,and pulmonary imaging is non-uniform exudative lesions.At present,the systemic inflammatory response after infection and trauma is the reason of ALI.Controlling the primary disease and curbing the systemic uncontrolled inflammatory response induced by it are necessary measures to prevent and treat ALI.Drug therapy is still treated with hormone anti-inflammatory and symptomatic treatment.Jinyin Qingre Oral Liquid(hereinafter referred to as JYQR)is a traditional Chinese medicine compound preparation developed by Hubei University of Traditional Chinese Medicine and Shiyan Taihe Hospital.This prescription has been proved to have the functions of clearing away heat and toxic materials,promoting blood circulation and cooling blood.Clinical application found that JYQR is effective in treating fever,lung inflammation,and tissue damage caused by respiratory infections caused by pathogenic microorganisms.This topic is to study the pharmacodynamics and mechanism of preventing and treating LPS-induced acute lung injury in mice.Objective:To investigate the preventive effect and mechanism of JYQR on mouse model of acute lung injury induced by lipopolysaccharide(LPS,a component of the outer wall of Gram-negative bacterial cell walls,and a substance composed of lipids and polysaccharides),for clinical application Provide theoretical basis.Method:1.Preparation of JYQR and screening of drug concentrationJYQR(each m L is equivalent to 1 g of native medicinal materials)was prepared according to the JYQR hospital homemade preparation process approved by Hubei Food and Drug Administration,and quality inspection was performed according to quality control standards.C57BL/6 mice were randomly divided into normal control group,model group,and JYQR(low,medium,and high dose)groups.After modeling and intervention,the Bronchoalveolar Lavage Fluid in each group was collected and used.The cell counter and BCA protein detection method were used to determine the total cell number and total protein content in BALF.Respectively,to determine the optimal JYQR dosage.2.JYQR for prevention and treatment of LPS-induced acute lung injury in miceTo investigate the preventive and therapeutic effects of JYQR on mouse models of acute lung injury,to study the preventive effects of JYQR before pre-modeling and to treat,and to study the therapeutic effects of post-modeling.The two experiments were randomly divided into four groups,the normal control group,the model group,the JYQR group,and the dexamethasone group.After modeling and intervention in each group,BALF and lung tissue samples were collected.The hematoxylin-eosin staining method was used to observe the pathological damage of the lung tissues of mice,the total cell number in BALF was measured by a cell counter,the protein content in BALF was detected by BCA method,and the Ig M content in BALF was detected by ELISA method.3.Effect of JYQR on NF-?B signaling pathway in mice with acute lung injuryBALF and lung tissue samples of normal control group,model group,JYQR group and dexamethasone group were taken,and the contents of inflammatory factors IL-1?,IL-6 and TNF-? in BALF were detected by ELISA.Western blot was used to detect the expression of NF-?B signaling pathway-related proteins I?B,NF-?B p65 and their phosphorylation in lung tissue.Immunohistochemistry was used to detect the expression of NF-?B p65 protein and to locate the protein expression.Result:1.Preparation of JYQR and determination of drug concentrationThe quality test results of JYQR showed that the prepared JYQR met the quality standards approved by the Food and Drug Administration of Hubei Province.The experimental results of the concentration of drug showed that compared with the model group,after high-dose JYQR(16 g/Kg)intervention,the total cell number and protein content of BALF in mice were significantly reduced(p <0.01).2.Prevention and treatment effect of JYQR on LPS-induced acute lung injury in miceThe results of the JYQR preventive effect experiment showed that compared with the model group,the lung injury of the mice in the JYQR group was significantly improved,and the total cell number,total protein content,and Ig M content in BALF were significantly reduced(p<0.05).There was no significant difference between the effect and dexamethasone(p>0.05).The experimental results of the treatment effect of JYQR showed that compared with the model group,the lung tissue damage of the mice in the JYQR group was significantly improved,and the total cell number,total protein concentration,and Ig M content in BALF were significantly reduced(p<0.05).There was no significant difference between the effect and dexamethasone(p>0.05).3.JYQR inhibits NF-?B signaling pathway in mice with acute lung injuryCompared with the model group,the levels of IL-1?,IL-6,and TNF-? in BALF in the JYQR prevention and treatment groups of mice were significantly reduced(p<0.05),compared with dexamethasone No significant difference(p>0.05).Western blot results showed that compared with the normal control group,the phosphorylation ratios of NF-?B p65 and I?B proteins in the lung tissue of the model group were significantly increased(p<0.05);compared with the model group,The phosphorylation ratio of NF-?B p65 and I?B protein in JYQR prevention group and treatment group was significantly decreased(p<0.05).Immunohistochemical results showed that compared with the normal control group,the expression of NF-?B p65 in the nucleus of the lung tissue of the model group was significantly increased(p<0.05);compared with the model group,the nucleus of the lung tissue in the JYQR prevention group and the treatment group was significantly increased.NF-?B p65 expression was significantly decreased(p<0.05).Conclusion:1.The experimental preparation of JYQR meets relevant standards.The high-dose JYQR group has obvious effects on lung injury.Therefore,the concentration of JYQR was selected to be 16 g / Kg.2.JYQR has a good preventive and therapeutic effect on LPS-induced acute lung injury mice,which can significantly down-regulate the expression of IL-1?,IL-6,TNF-? inflammatory factors,improve the degree of lung tissue lesions,and improve alveolar capillary Vascular permeability.3.The mechanism of JYQR in preventing and treating acute lung injury may be related to the inhibition of NF-?B signaling pathway. |
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