Investigate The Antioxidant And Anti-inflammatory Effects Of Lycopene On Bronchial Asthma Through The Nrf2/ARE/HO-1 Pathway

Research background :Bronchial asthma(abbreviated as "asthma")is a chronic disease characterized by airway inflammation and hyperresponsiveness,mainly manifested by chronic inflammation of the airways,reversible airflow restriction,airway hyperresponsiveness to many stimuli,and a series of changes in airway structure with increasing course-airway reconstruction.Clinically characterized by repeated wheezing and shortness of breath,with or without symptoms of chest tightness and cough.The onset of asthma is complex and predisposed to polygenetics.Although the etiology of asthma is not fully clear,the mechanisms that have been recognized include airway immunological mechanisms and neuromodulation mechanisms.However,asthma is still an irreversible disease and good clinical relief can only be achieved with effective treatment.Asthma is a very serious problem affecting global health,with increasing prevalence in many countries and regions,and is more prevalent and more common than in other groups in children.Although the proportion of hospitalizations and deaths from asthma in some countries is lower than in the past,they still place a huge burden on healthcare systems and society,so research into asthma-related treatments is extremely needed.There is growing evidence that transcription factor Nrf2(Nuclear Factor erythroid 2-Related Factor 2)plays a key role in controlling the expression of antioxidant genes that ultimately exert anti-inflammatory functions.Nrf2 and keap1(Kelch Like ECH Associated Protein 1)are key factors in intracellular redox homeostasis and inflammation regulation,and studies have shown that Nrf2 can effectively regulate the heme oxygenase-1(HO-1)axis,thereby acting as an anti-inflammatory and antioxidant effect.The latest study has found a close correlation between the Nrf2 antioxidant response element system and the expression of inflammatory mediators.Lycopene,one of the carotenoids and red pigments found in plant foods,has a strong antioxidant capacity although it does not have the physiological activity of vitamin A.However,at present,there are not many studies on lycopene-induced Nrf2/ARE/HO-1 signaling pathway for ovalbumin-induced asthma mouse models.The objective of this project is to investigate the antioxidant and anti-inflammatory effects of lycopene on bronchial asthma by regulating the Nrf2/ARE/HO-1 pathway.Materials and Methods:BALB/c mice were selected,6-8 weeks old.Based on the random numbers generated by SPSS,the experimental mice were divided into four groups: control group(SAL),model group(OVA),solvent group(COR),and lycopene group(LYC),ten in each group,in order to perform more accurate experiments.Except for the SAL group,the remaining mice in each group were intraperitoneally injected with 20 μg OVA(emulsified in 1 mg aluminum hydroxide)on days 1,7,and 14,and mice in the SAL group were intraperitoneally injected with the same amount of normal saline(NS).Then,from day 21,atomize five times every other day.The OVA group and the LYC group were atomized with 25 ml of OVA(concentration of 1%)for 30 min.The LYC group was given 100 mg/kg lycopene gavage dissolved in 0.2 ml corn oil half an hour before each excitation,and 0.2 ml of lycopene gavage half an hour before each excitation in the OVA group.The SAL group was given 25 ml NS nebulization for 30 min(0.2ml NS gavage half an hour before each excitation);The COR group was given 25 ml NS nebulization for 30 min(0.2ml corn oil was given half an hour before each excitation);Each group of mice is sacrificed within 24 h of the last excitation.The lavage solution and whole blood were collected,the supernatant was taken after centrifugation,and the ELISA method was used to determine Ig E,OVA-specific Ig E and their cytokines IL-4,SOD,CAT and other indexes.At the same time,the whole blood inflammatory cells of mice were counted and classified to determine asthma-related indicators.Finally,tissue sections were made from the anterior lobe of the right lung and HE staining was performed to clarify the lung tissue lesions.The remaining lung tissues were subjected to immunohistochemical staining,fluorescence quantitative PCR and Western Blot to determine the ability to express Nrf2,HO-1,COX-2 and TNF-α proteins in lung tissue,and fluorescence quantitative PCR to determine the expression of these genes at the m RNA level.Results:OVA intraperitoneal injection combined with nebulisation can establish a mouse model of bronchial asthma.Lycopene attenuated the inflammatory response and acted as an antioxidant in mice.Improvement of lung histopathological damage,possibly through activation of the Nrf2/ARE/HO-1 pathway.Conclusion:1.Intraperitoneal injection of ovalbumin combined with nebulized inhalation can successfully construct a mouse model of asthma.Lycopene has a protective effect against both oxidative stress and inflammatory damage.2.The study suggests that Lycopene may exert antioxidant and anti-inflammatory functions through regulating the Nrf2/ARE/HO-1 pathway,thus effectively inhibiting the onset of asthma in mice.