The Expression Of Hypoxia Inducible Factor-1α In Peripheral Blood Mononuclear Cells Of Patients With Chronic Obstructive Pulmonary Disease

Objectives To investigate the expression of HIF-1αin peripheral blood mononuclear cell(PBMC) in patients with chronic obstructive pulmonary disease (COPD) and the relationshipsbetween expression level of HIF-1αin PBMC and serum level in C reactive protein (CRP), lungfunction, indexes of arterial blood gas analysis. To explore the role of HIF-1αin the onset andprogression of COPD and whether it can be used as a marker of pathogenetic condition of thisdisease and effect of therapy.Methods1. Subjects The subjects were divided into three goups: 50 stable COPD patients, 50 patientswith acute exacerbation of COPD(AECOPD) and healthy subjects. COPD patients were from theDepartment of Respiratory Medicine and Outpatient of Guangdong General Hospital and healthysubjctes from the Healthcare Center of Guangdong General Hospital from May 2009 to June2010.2. HIF-1αprotein detection PBMC were separated by Lymphocytes Separation Mediumand cell protein were extracted by RIPA.The HIF-1αprotein were measured by Western blot.3. Serum C-reactive protein (CRP) levels detection Serum C-reactive protein (CRP)levels were Detected in the laboratory department in our hospital4. Arterial blood gas analysis Arterial partial pressure of oxygen(PO2),arterial partialcarbon dioxide(PCO2)5. Pulmonary function test Forced expiratory volume(FVC) and the ratio of FVC andpredicted value(FVC%), FEV1, FEV1% and FEV1/FVC were detected in the pulmonary function test.6. Statistical analysis SPSS 13.0 software package was used for statistical analysis.Variances of successive type were presented as mean±standard deviation.χ2-test was used fordifference of gender among the three groups. One-way analysis of variance was used fordifferences among the three groups. LSD-t tset was used for multiple comparison in varianceswith homogeneity and Dunnett's T3 test in variances without homogeneity. Independent-T testwas used for differences between stble COPD patients and AECOPD patients. Bivariatecorrelations were performed to evaluate the relationship between the expression level ofHIF-1αand other indexes. A value of P less than 0.05 was considered as statistical significance.Results1. Clinical characteristicsAges in stable COPD patients, AECOPD patients and healthy subjects were (65.32±6.55)yearsold, (66.22±2.62) years old and (65.03±6.37) years old respectively and there was no significantdifference in the three groups. There were 50 stable COPD patients with 40 males and 10females, 50 AECOPD patients with 40 males and 10 females and 30 healthy subjecs with 20males and 10 females. There was no significant difference of age among the three groups.2. Expression-levels of HIF-1αThe levels of HIF-1αin PBMC in stable COPD patients, AECOPD patients and healthy subjectswere (0.46±0.07), (0.78±0.07), (0.16±0.08) respectively and there was significant difference inthe three groups (F=709.39, P<0.001). The multiple comparison between stable COPD patientsand healthy subjects (P<0.001), the one between AECOPD patients and healthy subjects(P<0.001) and the one between stable COPD patients and AECOPD patients (P < 0.001)werestatistically significant.3. Serum CRP levelsThe serum CRP levels in stable COPD patients, AECOPD patients and healthy subjects were(5.81±1.34)mg/L, (41.20±19.31)mg/L, (3.07±1.03)mg/L respectively and there was significantdifference in the three groups (F=141.403, P<0.001). The multiple comparison between stableCOPD patients and healthy subjects (P < 0.001) and the one between AECOPD patients andhealthy subjects (P<0.001) and the one between stable COPD patients and AECOPD patients (P <0.001) were statistically significant.4. Arterial blood gas analysisThe levels of PO2 in stable COPD patients, AECOPD patients and healthy subjects were(10.21±1.45)kPa, (8.84±0.67) kPa,(13.37±0.65) kPa respectively and there was significantdifference in the three groups (F=441.103, P<0.001). The multiple comparison between stableCOPD patients and healthy subjects(P < 0.001)and the one between AECOPD patients andhealthy subjects(P<0.001)and the one between stable COPD patients and AECOPD patients (P<0.001)were statistically significant. The levels of PCO2 in stable COPD patients, AECOPDpatients and healthy subjects were (4.30±0.6)kPa, (6.21±0.64)kPa,(4.33±0.31)kPa respectivelyand there was significant difference in the three groups (F=163.070, P<0.001). The multiplecomparison between AECOPD patients and healthy subjects(P < 0.001)and the one betweenstable COPD patients and AECOPD patients (P<0.001)were statistically significant, but the onebetween stable COPD and healthy subjects were no statistically significant.5. Correlations between HIF-1αin PBMC and serum CRP level, indexes of arterialblood gas analysis , lung function in stable COPD patientsHIF-1αin PBMC correlated positively with CRP (r =0.372, P=0.008). HIF-1αcorrelatedinversely with PO2 (r = -0.670, P<0.001). HIF-1αin PBMC correlated positively with PCO2(r=0.453, P<0.001). HIF-1αin PBMC correlated positively with FEV1%(r = -0.774, P<0.001).There was no significant correlation between HIF-1αin PBMC and FEV1, FVC%, FVC orFEV1/FVC respectively.6. Correlations between HIF-1αin PBMC and serum CRP level, lung function,indexes of arterial blood gas analysis in AECOPD patientsHIF-1αin PBMC correlated positively with rerum level of CRP (r =0.471, P=0.001). HIF-1αinPBMC correlated inversely with PO2(r = -0.780, P < 0.001). HIF-1αin PBMC correlatedpositively with PCO2 (r = 0.446, P=0.001).Conclusions1. The expression of HIF-1αin PBMC significantly increased in COPD patients, with theexacerbation of copd,the expression was increased. 2. The expression level of HIF-1αin AECOPD patients and stable COPD patients werecorrelated with the status of systemic inflammation.3. The expression level of HIF-1αin AECOPD patients and stable COPD patients werecorrelated with the hypoxia and carbon dioxide retention.4. The expression level of HIF-1αin stable COPD patients were correlated with the degree offlow limitation.