中国病理生理杂志2026，Vol.42Issue(8)：1506-1515,10.DOI:10.3969/j.issn.1000-4718.2026.08.004
香烟烟雾暴露与脂多糖滴注联合诱导的慢性阻塞性肺疾病大鼠认知功能损伤的评价
Evaluation of cognitive impairment in rats with chronic obstructive pul-monary disease induced by combined cigarette smoke exposure and in-tratracheal lipopolysaccharide instillation
摘要
Abstract
AIM:This study aimed to investigate cognitive function in rats with chronic obstructive pulmonary disease(COPD)induced by cigarette smoke exposure and bacterial lipopolysaccharide instillation,and explore the role of the inflammatory response in cognitive impairment.METHODS:SPF Wistar rats were randomly divided into blank and model groups.The model group was established by cigarette smoke exposure and intratracheal lipopolysaccharide instilla-tion.At 24 h after the final smoke exposure,open field,Y-maze,novel object recognition,and pulmonary function tests were performed.The serum and hippocampal tissue interleukin-1β(IL-1β),IL-6,and tumor ncerosis factor-α(TNF-α)levels were measured by ELISA.Pathological changes in the lung and hippocampus were observed using hematoxylin-eo-sin(HE),Masson and Nissl staining.Ionized calcium-binding adapter molecule-1(Iba-1)expression was detected by im-munohistochemistry.RESULTS:Compared with blank group,the rats in model group showed a slower increase in body weight,significant decrease in locomotor activity in the open-field test,significant reductions in the number of arm entries and spontaneous alternation rate in the Y-maze test,and decreased discrimination index in the novel object recognition test.In model group,forced expiratory volume in 0.3 s(FEV0.3)and FEV0.3/forced vital capacity(FVC)were significant-ly reduced.HE staining of the lung tissue revealed emphysema-like changes and inflammatory infiltration in the model group,whereas Masson staining showed blue-stained collagen fiber deposition in the lung tissue.The levels of TNF-α,IL-1β and IL-6 of serum and hippocampal tissues were elevated.HE and Nissl staining of the hippocampus indicated aggra-vated neuronal damage in the model group,characterized by neuronal pyknosis and necrosis in the CA1 region,along with dispersed and condensed Nissl bodies.Immunohistochemistry revealed a significantly increased expression of Iba-1-posi-tive cells in the hippocampal CA1 region of the model group.CONCLUSION:Rats with COPD induced by cigarette smoke exposure combined with lipopolysaccharide instillation exhibit cognitive impairment,neuronal damage,and high expression of Iba-1-positive cells in the hippocampal CA1 region.The levels of inflammatory factors,such as TNF-α,IL-1β and IL-6,were elevated in both serum and hippocampal tissue.Therefore,a cascade reaction involving systemic and central nervous system inflammation may play a key role in the cognitive impairment associated with COPD.关键词
慢性阻塞性肺疾病/认知功能损伤/大鼠模型/海马/炎症Key words
chronic obstructive pulmonary disease/cognitive impairment/rat model/hippocampus/inflam-mation分类
医药卫生引用本文复制引用
韩昕昱,张逸馨,冯婧丽,金政杰,何家恺,冯淬灵..香烟烟雾暴露与脂多糖滴注联合诱导的慢性阻塞性肺疾病大鼠认知功能损伤的评价[J].中国病理生理杂志,2026,42(8):1506-1515,10.基金项目
国家重点研发计划(No.2025YFC3508202) （No.2025YFC3508202）
国家自然科学基金资助项目(No.82374361) （No.82374361）
北京中医药大学教育研究科学课题(No.XBB24056) （No.XBB24056）
