药学研究2025，Vol.44Issue(8)：729-736,8.DOI:10.13506/j.cnki.jpr.2025.08.001
花形乳糖装载PEG修饰姜黄素固体脂质纳米粒吸入微粉对COPD小鼠肺组织中炎症因子、ACE2表达变化的影响
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
摘要
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.关键词
姜黄素/聚乙二醇修饰固体脂质纳米粒/慢性阻塞性肺疾病/炎症因子/血管紧张素转换酶2Key words
Curcumin/PEG modified solid lipid nanoparticles/Chronic obstructive pulmonary disease/Inflammatory factor/ACE2分类
医药卫生引用本文复制引用
李旭,王梓,郝迪,李楠..花形乳糖装载PEG修饰姜黄素固体脂质纳米粒吸入微粉对COPD小鼠肺组织中炎症因子、ACE2表达变化的影响[J].药学研究,2025,44(8):729-736,8.基金项目
国家自然科学基金项目(No.81903565) （No.81903565）
天津市自然科学基金项目(No.21JCYBJC01630、23JCYBJC00410) （No.21JCYBJC01630、23JCYBJC00410）
天津市卫生健康委中医中西医结合科研项目(No.2023102) （No.2023102）
