Na+/Ca2+交换抑制剂对慢性阻塞性肺疾病患者肺泡巨噬细胞功能的影响

目的观察Na /Ca2 交换抑制剂Benzamil对慢性阻塞性肺疾病(COPD)患者肺泡巨噬细胞(AM)胞浆中游离钙离子(〔Ca2 〕i)浓度及其对生成肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)的影响。方法采用支气管肺泡灌洗、细胞培养和荧光指示剂的方法,测定36例COPD稳定期患者及36例健康体检者AM内〔Ca2 〕i浓度及其生成的TNF-α和MDA含量。结果1COPD组患者AM内〔Ca2 〕i〔(68.26±7.24)nmol/L〕、TNF-α〔(5.74±0.42)ng/L〕和MDA〔(3.77±0.61)μg/L〕水平均较健康对照组〔分别为(60.61±6.26)nmol/L、(2.06±0.20)ng/L、(1.91±0.19)μg/L〕明显增高(P均<0.01);2给予缺氧后,COPD组AM内〔Ca2 〕i浓度〔(168.34±17.58)nmol/L〕、TNF-α〔(9.67±1.01)ng/L〕和MDA〔(11.21±1.01)μg/L〕水平均较刺激前增高(P均<0.01);3先加Benzamil孵育AM再缺氧,可使胞浆内〔Ca2 〕i浓度〔(129.21±14.33)nmol/L〕、TNF-α〔(6.78±0.52)ng/L〕和MDA〔(8.47±0.79)μg/L〕水平均较单纯缺氧时明显减少(P均<0.01)。结论Benzamil可抑制由缺氧引起AM内〔Ca2 〕i浓度增高及其产生的TNF-α、MDA含量;提示通过调节AM激活可抑制TNF-α、MDA的分泌。

Effect of Na+/Ca2+ exchange blocker, Benzamil, on alveolar macrophage function in patients with chronic obstructive pulmonary disease

OBJECTIVE: To observe the effect of Benzamil on cytosolic free calcium ions (Ca(2+)] i) concentration, tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) in alveolar macrophage (AM) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Alveolar macrophages were collected from bronchoalveolar lavage fluid, and they were cultured and Ca(2+)] i were determined by calcium fluorescent with indicator Fura-2/AM. The effects of Benzamil on the increase in cytosolic Ca(2+)] i and on secretion of TNF-alpha, MDA were investigated in 36 patients with COPD and 36 healthy volunteers. RESULTS: (1) Ca(2+)] i concentration (68.26+/-7.24) nmol/L, TNF-alpha (5.74+/-0.42) ng/L and MDA (3.77+/-0.61) microg/L were found in COPD patients, and they were significantly increased, as compared with the control group, in whom the contents were Ca(2+)] i concentration (60.61+/-6.26) nmol/L, TNF-alpha (2.06+/-0.20) microg/L, MDA (1.91+/-0.19) ng/L (all P<0.01). (2)The following data namely Ca(2+)] i concentration (168.34+/-17.58) nmol/L, TNF-alpha (9.67+/-1.01) ng/L and MDA (11.21+/-1.01) microg/L were obtained after anoxia in COPD patients (all P<0.01). (3)After incubation with Benzamil, and then subjected the cells to anoxia, the following data were obtained: Ca(2+)] i concentration (129.21+/-14.33) nmol/L, TNF-alpha content (6.78+/-0.52) ng/L and MDA (8.47+/-0.79) microg/L and they were all lower than only anoxia was applied (all P<0.01). CONCLUSION: Benzamil not only downregulates alveolar macrophages activity but also suppresses the generation of the TNF-alpha and MDA.