慢性阻塞性肺疾病大鼠呼吸、认知功能和海马区脑代谢物之间相关性研究

Correlation among respiratory function, cognitive function, and hippocampal metabolites in rats with COPD

目的探讨COPD模型大鼠呼吸功能、认知功能和海马区脑代谢物质子核磁共振波谱（、HNMR）特征变化的相关性，初步解释COPD引起认知功能损害的致病机制。方法建立COPD大鼠模型，同时设置对照组（n=12）。HE染色观察各组大鼠肺组织以及海马组织的病理学变化；测定FEV0.3、FVC、吸气阻力（RI）、动态顺应性（Cdyn）和FEV0.2。／FVC。血气分析仪测定大鼠血液中PaO2、PaCO2。Morris水迷宫实验测试大鼠学习记忆能力变化，利用’HNMR分析大鼠海马区N-乙酰天门冬氨酸（NAA）、胆碱复合物（Cho）、肌酸（cr）、肌醇（MI）和谷氨酸（Glu）水平。结果与对照组比较，COPD模型组大鼠肺泡扩张，间隔变窄、断裂，形成肺大疱，海马区组织椎体细胞脱落，排列疏松；同时COPD大鼠呼吸功能显著降低，认知功能显著减退；脑代谢物浓度均降低，其中NAA／Cr、Cho／Cr和Glu／Cr浓度降低差异具有统计学意义（t值为0．5572．387，P〈0．05）；COPD大鼠肺功能指标（FEV。／FVC和Cdyn）以及脑代谢物（NAA／Cr、Cho／Cr和Glu／Cr）与定位航行实验逃避潜伏期和空间探索实验逃避潜伏期均旱显著负相关，同时FEV。／FVC和Cdyn与NAA／Cr、Cho／Cr呈正相关。结论COPD大鼠呼吸功能衰退可改变海马区脑代谢物水平，从而可能引起认知功能降低。

Objective To study the correlation among respiratory function, cognitive function, and hippocampal metabolites on changes of concentration detected by proton nuclear magnetic resonance spectroscopy （1 HNMR） in rats model with chronic obstructive pulmonary disease （COPD） ,and propose a preliminary explanation to the pathogenesis of cognitive impair caused by COPD. Methods COPD rats model was established,and control group was set up （ n 12）. Pathologic changes in hippocampus and lung of rats was observed through HE stain. 0.3 s forced expiratory volume （FEV0.3）, forced vital capacity （FVC）, resistance index （RI）, dynamic compliance （Cdyn）, and FEV0 a/FVC were measured. Blood oxygen partial pressure （PaO2） and partial pressure of carbon dioxide （PaCO2） were determined in the blood of rats using blood gas analyzer. Morris water maze was used to evaluate the ability of learning and memory of rats. Levels of n acetyl aspartate （NAA）, choline compounds （Cho）, creatine （Cr） , myoinositol （MI） and glutamate （Glu） in rat hippocampus were analyzed byHNMR. Results In comparison with control group,alveolar expansion, narrow interval, fracture, and formation of pulmonary bulla were observed in lung, and the drop of vertebral body cell and loose arrangement in hippocampus tissue. Simultaneously, respiratory function and cognitive function were significantly lower in the group of COPD rats model. Concentration of cerebral metabolites, such as NAA/Cr, Cho/Cr and Glu/Cr, significantly decreased as compared to control group （with t values from 0. 557 to 2. 387, P 〈0.05）. In COPD model,significant negative correlation was observed between lung function indexs （FEV0 3/FVC and Cdyn） as well as cerebral metabolites （NAA/Cr, Cho/Cr and Glu/Cr） and not only navigation experiment escape latency but also space exploration escape latency, and at the same time lung these function indexs displayed a positive correlation with NAA/Cr and Cho/Cr. Conclusions The recession of respiratory function caused by COPD could change levels of cerebral metabolites in the hippocampus,and may impair cognitive function thereby.