Objective To explore effects of edaravone on apoptosis and expressions of apoptotic proteins Smac and XIAP in hippocampal CA1 pyramidal cell of rats under intermittent hypoxia. Methods A total of 96 adult male Wistar rats were randomly divided into control group, 5% intermittent hypoxic group and edaravone group, and each group was divided into 4 time groups at 7 d, 14 d, 21 d and 28 d, respectively, with 8 rats in each subgroup. The content of reactive oxygen species (ROS) in hippocampal tissues of the experimental rats was detected by the reactive oxygen species detection kit. Immunohistochemistry and Western blot were used to detect the expressions of Smac and XIAP protein in hippocampal CA1 region. The Tunel method detected the apoptosis of neurons. Results Compared with the control group, the content of ROS, the expressions of Smac and XIAP proteins and the neuronal apoptosis index in the hippocampus were increased in the 5% intermittent hypoxia group and the edaravone group at each time point (all P<0.05). The content of ROS, the Smac protein expression and the neuronal apoptosis index in the edaravone group were significantly lower than those in the 5% intermittent hypoxia group (all P<0.05). The expression of XIAP protein in the edaravone group was significantly higher than that in the 5% intermittent hypoxia group (P<0.05). Conclusion Edaravone may improve the antioxidant capacity of the body by scavenging oxygen free radicals and regulate Smac and XIAP- mediated apoptosis, thus playing a protective role on neurons.
Objective To explore the correlation of protein and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and serum amyloid A protein (SAA) with cognitive function in chronic obstructive pulmonary disease (COPD) patients with or without hypoxemia, in order to identify the serum indexes of early cognitive impairment in patients with COPD, and investigate the effect of hypoxemia on cognitive impairment. Methods Sixty-two COPD patients admitted in the respiratory department of Affiliated Hospital of North China University of Science and Technology from January 2013 to January 2017 were included in the study. The COPD patients were divided into a hypoxemia group (25 cases) and a non-hypoxemia group (37 cases) according to blood gas analysis. Meanwhile 30 healthy subjects were recruited as control. ELISA was used to measure the concentration of serum MCP-1 and SAA in all subjects, and RT-PCR was used to detect the mRNA expression of MCP-1 and SAA in peripheral blood mononuclear cells. Montreal cognitive assessment scale (MoCA scale) was used to determine cognitive function. The expression levels of MCP-1 and SAA were compared between three groups, and the correlations with cognitive dysfunction were analyzed. Results The expression levels of serum MCP-1 and SAA had the same trend as those of MCP-1 mRNA and SAA mRNA in peripheral blood in the COPD patients. The protein and mRNA levels of MCP-1 and SAA were higher than those in the healthy control group (all P<0.05). The COPD hypoxemia group and the COPD non-hypoxemia group were lower than the control group in MoCA score, and the MoCA score of the COPD hypoxemia group decreased more obviously (allP<0.05). The protein and mRNA levels of SAA and MCP-1 were negatively correlated with MoCA score (allP<0.05). Conclusion The protein and mRNA levels of MCP-1 and SAA in peripheral blood increase in COPD patients, and hypoxemia may be involved in cognitive dysfunction in COPD patients.
ObjectiveTo investigate the correlation and clinical significance of 8-hydroxydeoxyguanosine (8-OHdG) and endothelin-1 (ET-1) levels with cognitive dysfunction in patients with chronic obstructive pulmonary disease (COPD), and provide new idea for the prevention and treatment for cognitive dysfunction in COPD patients.MethodsA total of 103 COPD patients, according to the Montreal cognitive assessment scale standard for evaluation, were divided into a cognitive dysfunction group and a cognitive normal group. Serum 8-OHdG and ET-1 levels were compared between the two groups and their correlations with cognitive function were analyzed with the receiver operating characteristic (ROC) curve.ResultsThe levels of serum 8-OHdG and ET-1 in the COPD patients with cognitive impairment were significantly higher than those in the cognitive normal group ［8-OHdG: (13.91±9.04) ng/ml vs. (7.28±3.00) ng/ml; ET-1: (95.64±57.66)pg/ml vs. (69.20±7.89)pg/ml］ (both P<0.05). The levels of 8-OHdG (OR=22.94, 95%CI 7.06-74.53) and ET-1 (OR=19.76, 95%CI 6.59-59.31) were associated with cognitive impairment in the COPD patients. The areas under ROC curve of serum 8-OHdG and ET-1 levels to predict cognitive dysfunction in the COPD patients were 0.786 (95%CI 0.691-0.881) and 0.790(95%CI 0.695-0.885).ConclusionsThe serum levels of 8-OHdG and ET-1 are associated with cognitive impairment in COPD patients. The levels of 8-OHdG and ET-1 in serum can predict cognitive impairment with high specificity.
ObjectiveTo investigate the expression of C/EBP homologous protein (CHOP) in lung tissue of chronic intermittent hypoxia rats, and explore the intervention effect of edaravone and its possible mechanism.MethodsA total of 120 adult male Wistar rats were randomly divided into three groups: a normal control group (UC group), a chronic intermittent hypoxia group (CIH group), an edaravone intervention group (NE group), and a normal saline group (NS group). The above four groups were also randomly divided into five time subgroups of 3 days, 7 days, 14 days, 21 days and 28 days, respectively, with 6 rats in each time subgroup. The histopathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining and the expression of CHOP in lung tissue was detected by immunohistochemical method.ResultsHE staining results showed that there was no obvious pathological change in UC group. The epithelial cells of lung tissue in CIH group showed edema, hyperemia, widening of alveolar septum and inflammatory cell infiltration. The pathological injury was more serious with the prolongation of intermittent hypoxia time. There were also pathological changes in NE group, but the degree of lung tissue injury was significantly lower than that in CIH group. The results of immunohistochemistry showed that the expression of CHOP in CIH group was significantly higher than that in UC group. The expression of CHOP in NE group was higher than that in UC group, but it was still significantly lower than that in CIH group.ConclusionsThe expression of CHOP protein in lung tissue of chronic intermittent hypoxic rats is enhanced and the high expression of CHOP protein plays a certain role in the lung injury of chronic intermittent hypoxia rats complicated with lung injury. Edaravone may protect lung tissue from chronic intermittent hypoxia by inhibiting the expression of CHOP.
Objective To observe the relationship of serum levels of homocysteine (HCY) and chemokine C-C motifligand 2 (CCL2) with cognitive impairment in COPD patients with different degrees of emphysema. Methods Sixty-twoCOPD patients identified according to emphysema phenotype classification and admitted from January 2016 to March 2017 were recruited in the study. There were 37 cases in emphysema 1-2 grade and 25 cases in emphysema 3-4 grade. Simultaneous 30 healthy subjects undergoing physical examination were recruited as control. Montreal cognitive assessment (MoCA) scale investigation and serum HCY and CCL2 test were completed. Relationship analysis was conducted on serum HCY, CCL2 levels with cognitive impairment in the COPD patients with different degrees of emphysema. Results Compared with the 1-2 grade subgroup, the PaO2 was lower, PaCO2 was higher, the plasma HCY and CCL2 levels increased in the 3-4 grade subgroup with significant differences (all P<0.05). MoCA total score and subscores were relatively low in the COPD group with emphysema than the control group (except visuospatial ability scores in the 1-2 grade subgroup). MoCA scores were statistically lower in the 3-4 grade subgroup than those in the 1-2 grade subgroup (allP<0.05). Correlation analysis showed that HCY and CLL2 levels were negatively correlated with MoCA scores and subscores (P<0.01), and HCY and CLL2 were positively correlated (bothP<0.01). The area under the receiver operating characteristic curve of HCY and CLL2 for evaluating cognitive impairment was 0.79 and 0.97, respectively. Conclusion In patients with different degrees of emphysema phenotype, serum HCY and CCL2 levels are increased in different degree, and the degree of emphysema is closely related with cognitive dysfunction.