Effects of flower-shaped lactose loaded PEG-modified curcumin solid lipid nanoparticles on the expression of inflammatory factors and ACE2 in lung tissue of COPD mice

LI Xu; WANG Zi; HAO Di; LI Nan

doi:10.13506/j.cnki.jpr.2025.08.001

Abstract：Objective To investigate the therapeutic effect of inhaling flower-shaped lactose loaded with PEG modified curcumin solid lipid nanoparticles on pulmonary inflammation in mice with chronic obstructive pulmonary disease induced by lipopolysaccharide and cigarette smoke,and to reveal its molecular mechanism.Methods Mouse COPD model was established by nasal instillation of LPS and inhalation of CS,and 10 mice were randomly selected as normal control group.The remaining 50 mice were randomly divided into model group,budesonide group(20 mg·kg-1)and PEG-Cur-FL high-dose and low-dose groups(40,20 mg·kg-1)after intranasal infusion of LPS.From the fifth week,all mice with intranasal infusion of LPS were smoked twice a day,with 1 hour rest every other day,and the COPD model was reproduced for 4 months.From the 17th week,mice in each group were given corresponding drugs through trachea once a day for 28 days.Twenty-four hours after the last administration,bronchoalveolar lavage fluid(BALF)was collected and the white blood cells were classified and counted.The concentrations of IL-1β and IL-6 in BALF of mice were detected by ELISA kit.Hematoxylin-eosin(HE)staining and Masson staining were used to detect the pathological morphology of trachea and lung tissue and the deposition of collagen fibers in lung tissue.Immunohistochemical method was used to detect the positive expression of tumor necrosis factor-α and matrix metalloproteinase-2(MMP-2)in lung tissue.Western blotting was used to detect the protein expressions of angiotensin converting enzyme 2(ACE2)and IL-6 in lung tissue.Results Compared with the normal control group,the total number of white blood cells,neutrophils,lymphocytes,monocytes,eosinophils and basophils in BALF of COPD mice induced by LPS+CS increased significantly(P＜0.01).The contents of IL-6 and IL-1βinflammatory factors in BALF increased significantly(P＜0.01).Ciliary columnar epithelium hyperplasia,thickening and shedding were found in the bronchi of lung,mucus accumulation,alveolar structure disorder,inflammatory cell infiltration,tissue edema,and a large number of collagen fibers were found in alveolar septum and interstitial lung.The positive expression of TNF-α and MMP-2 in lung tissue was significantly enhanced(P＜0.01),the expression level of ACE2 receptor in lung tissue was significantly decreased(P＜0.05),and the expression level of IL-6 protein was significantly increased(P＜0.05).After pulmonary inhalation of PEG-Cur-FL,all the above indexes were obviously improved.Conclusion PEG-Cur-FL can alleviate the lung inflammatory reaction induced by LPS+CS in COPD mice,and its mechanism may be that it can reduce the synthesis and release of inflammatory factors and inhibit the synthesis and deposition of collagen by up-regulating the expression level of ACE2 receptor,thus effectively delaying the occurrence of lung tissue failure.