The Anti-Inflammatory and Antioxidant Mechanism of Sanchen Powder(三臣散)on Lung Inflammation in Young Rats Based on TLR4/NF-κB and Nrf2/p62 Pathways
Objective:To explore the anti-inflammatory and anti-oxidation effects of Sanchen powder(SCP)on lung inflammation induced by lipopolysaccharide(LPS)in young rats based on TLR4/NF-κB and Nrf2/p62 pathways.Methods:Totally 76 young rats were divided into blank group(n=12)and mold-making group(n=64).The young rats in the model-making group were induced pulmonary inflammation by oral and tracheal instillation of LPS,and the model rats were divided into high dose SCP group(HSCP group),low dose SCP group(LSCP group),dexamethasone group(DEX group)and model group(Model group).Each group consisted of 16 rats.Rats were given 0.10 g/mL SCP intragastric administration in HSCP group,and 0.05 g/mL SCP intragastric administration in LSCP group.Rats were given 0.025 g/mL DEX intragastric administration in DEX group and 1 mU100 g sodium carboxymethyl cellulose(CMC-Na)solution intragastric administration in Model group and blank group,twice a day.Samples were taken 24 h after the last dose on the day 2nd and day 4th respectively(n=8).After sampling,the success of modeling was detected by lung pathological sections.Then,12 animals were selected from each group(6 on the 2nd and 4th day respectively)for subsequent index detection.The general condition and body weight were observed.The four items of blood coagulation and blood routine were tested.HE staining was used to observe the pathology of lung tissue.Enzyme linked immunosorbent assay(ELISA)was used to detect the content of hypothalamic fever central mediator and the inflammatory factors of bronchoalveolar lavage fluid(BALF).The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in lung tissue were detected by biochemical method.The content of TLR4,IκBα,p65,Nrf2 and p62 protein in lung tissue was detected by Western blotting.Results:Compared with the blank group,a large number of inflammatory cells were infiltrated in the lungs,and alveolar structure was destroyed in Model group on the 2nd day;Alveolar wall was transparent,and alveolar wall was thickened and fused in Model group;And bronchial sheet exudates were found in Model group on the 2nd day.The alveolar wall thickened and the number of alveoli decreased in Model group,with pulmonary interstitial fibrosis on the 4th day.Compared with Model group,HSCP group,LSCP group and DEX group showed lower overall lung injury degree,and HSCP group showed the lowest.The Model group showed higher neutrophil count,prostaglandin E(PGE),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),TLR4 expression and MDA content than blank group on the 2nd day(P＜0.05),while lower cyclic adenosine phosphate(cAMP)and transforming growth factor-β(TGF-β)than blank group(P＜0.05).On 4th day,the Model group showed higher neutrophil number,PGE,IL-6,interleukin-4(IL-4),interleukin-10(IL-10),TNF-α and MDA contents than blank group(P＜0.05),while lower expressions of cAMP,TGF-β,IκBα and SOD level than blank group(P＜0.05).On the 2nd day,HSCP group showed higher cAMP and TGF-β than Model group,LSCP group and DEX group(P＜0.05 or P＜0.05),while lower PGE,IL-6,TNF-α,IL-4 and MDA than Model group,LSCP group and DEX group(P＜0.0 1 or P＜0.05).HSCP group showed higher IL-10 than Model group(P＜0.01),and higher TLR4 than LSCP group and DEX group(P＜0.05).DEX group showed lower TLR4 than Model group(P＜0.05).On the 4th day,HSCP group,LSCP group and DEX group showed higher cAMP,IL-10 and TGF-βthan Model group(P＜0.05 or P＜0.01),while lower contents of neutrophils,PGE,IL-6,TNF-α,IL-4 and MDA than Model group(P＜0.05 or P＜0.01).There was no significant difference in the expression levels of TLR4 and IKBα among all groups on the 4th day(P＞0.05).Conclusion:SCP can alleviate LPS-induced mild pneumonia in young rats,and its mechanism may be that it regulates the inflammatory factors downstream of TLR4/NF-κB pathway to inhibit the inflammatory response and that it activates the Nrf2/p62 pathway to regulate the factors related to oxidative stress to inhibit the oxidative stress response.
infantile pneumoniaSanchen poweranti-inflammatoryantioxidantyoung rat
万方数据
维普
