高原慢性阻塞性肺疾病合并慢性肺心病低氧血症与肿瘤坏死因子系统活性及对营养不良的影响

Relationship between chronic hypoxemia and activation of the tumor necrosis factor-α system in patients with chronic obstructive pulmonary disease associated chronic cor pulmonale at high altitude area

目的探讨高原地区慢性阻塞性肺疾病(COPD)合并慢性肺心病(CCP)患者低氧血症与肿瘤坏死因子-α(TNF-α)系统活性的关系,及对营养不良的影响。方法对高原地区(海拔2260～3500m)52例COPD合并CCP低氧血症缓解期患者测定了血清TNF-α和血浆可溶性肿瘤坏死因子受体-55(sTNF-R55)、1s用力呼气容积占预计值百分比(FEV1%)、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、体重(BW)、理想体重百分比(%NW)和体重指数(BMI),并与30名年龄相似的平原健康人作对照。结果 COPD合并CCP组BW、%NW、BMI、FEV1%和PaO2显著低于对照组,PaCO2、血清TNF-α和血浆sTNF-R55显著高于对照组(均P<0.01)。COPD合并CCP组PaO2水平与血清TNF-α、血浆sTNF-R55水平呈显著负相关(TNF-α:r=-0.787,P<0.01;sTNF-R55;r=-0.802,P<0.01),TNF-α、sTNF-R55与BMI呈显著负相关(TNF-α:r=-0.785,P<0.01;sTNF-R55:r=-0.791,P<0.01),TNF-α与sTNF-R55水平呈显著正相关(sTNF-R55;r=0.702,P<0.01)。COPD合并CCP患者中,PaO2<45mmHg亚组TNF-α、sTNF-R55水平显著高于PaO2≥45mmHg亚组(均P<0.01);BMI<18.0kg/m2亚组的TNF-α、sTNF-R55水平显著高于≥18.0kg/m2亚组(均P<0.01);BMI<18.0kg/m2患者PaO2<45mmHg亚组的TNF-α、sTNF-R55水平显著高于PaO2≥45mmHg亚组(均P<0.05)。结论高原COPD合并慢性肺心病全身低氧血症患者体内肿瘤坏死因子-α系统活性增强,这可能是导致本病患者发生营养不良的重要因素。

Objective To assess the relationship between chronic hypoxemia and activation of the tumor necrosis factor-α （TNF-α） system in patients with chronic obstructive pulmonary disease （COPD） associated chronic cor pulmonale （CCP） at high altitude area. Methods The levels of serum TNF-α, plasma soluble TNF-receptor55 （ sTNF-R55 ） , forced expiratory volume in 1 second expressed as percentage predicted （ FEV1% ） , partial pressure of artery blood 02 （ PaO2 ） , partial pressure of in artery blood CO2 （ PaCO2 ） , body weight （ BW ） , percent of normal body weight （ % NW ） and body mass index （ BMI ） were measured in 52 patients with stable COPD associated CCP at high altitude area, and 30 agematched healthy controls at 400 m above sea levels.Results The BW, % NW, BMI, FEV, % and PaO2 were significantly lower, and PaCO2, TNF-α, sTNF-R55 were significantly higher in patients with COPD associated CCP group than those in control group （ all P 〈 0.01 ）. In patients with COPD associated CCP group, there was both inverse correlations between PaO2 with TNF-α and sTNF-R55 levels （ TNF-α ：r = - 0. 787, P 〈 0.01, sTNF- R55：r = -0. 802,P 〈 0.01 ）, there was both inverse correlations between levels of TNF-α and sTNF-R55 with BMI（TNF-α：r = -0. 785 ,P 〈0.01 ,sTNF-R55 ：r = -0. 791, P 〈 0. O1 ） ,TNF-α level correlated well with sTNF-R55 levels （ sTNF-R55 ： r = 0. 702, P 〈 0.01 ）. In patients with COPD associated CCP group, levels of TNF-α and sTNF-R55 were significantly higher in PaO2 〈 45 mm Hg subgroup than those in PaO2 ≥45 mm Hg subgroup （ all P 〈 0.01 ） , levels of TNF-α and sTNF-R55 were significantly higher in BMI 〈 18.0 kg/m2 subgroup than those in BMI ≥ 18.0 kg/m2 subgroup （all P 〈 0.01 ）. Levels of TNF-α and sTNF-R55 were significantly higher in the PaO2 〈 45 mmHg subgroup than those in PaO2 ≥45 mm Hg subgroup in patients with BMI 〈 18.0 kg/m2 （all P 〈 0. 05 ）. These relationships were not observed in the healthy controls. Conclusions Systemic hypoxemia noted in patients with COPD associated CCP is associated with activation of TNF-α system in vivo, which may be a factor contributing to the malnutrition in patients with the disease at high altitude.