地塞米松对博莱霉素致肺间质纤维化大鼠肺内炎性细胞的影响

目的　探讨地塞米松 (dexamethasone,DXM )能否通过诱导肺内炎性细胞凋亡而减轻博莱霉素所致大鼠肺间质性纤维化。方法　 75只SD大鼠随机分为对照组 (C组 )、博莱霉素组 (BLM组 )和地塞米松组 (DXM组 )。于实验的第 1、3、7、14和 2 8天处死动物 ,获取肺泡灌洗液 (BALF) ,行细胞计数、分类、流式细胞仪测定DNA亚二倍体含量 ;观察肺泡炎和肺纤维化程度及凋亡细胞形态 ;DNA片段原位缺口末端标记 (TUNEL)法进行肺组织凋亡细胞半定量。结果　 ( 1)BALF细胞计数 :不同时间DXM组均低于BLM组 ,P均 <0 .0 5 ;( 2 )BALF细胞分类 :DXM组中性粒细胞比例除第 1天组外 ,其余各相应时间组均比BLM组明显降低 ,P <0 .0 1;( 3)BALF细胞中凋亡细胞所占比例 :DXM第 14、2 8天组均明显高于相应时间的BLM组 ,P <0 .0 5 ;( 4 )DXM组肺泡炎高峰较BLM组后移 ;纤维化程度也明显低于BLM组 ;( 5 )形态学观察 :DXM各时间组与BLM组比较 :凋亡细胞明显增多 ;BLM 2 8d组肺泡间质胶原明显多于DXM组 ,纤维母细胞增多 ;( 6 )肺组织炎性细胞凋亡指数 :DXM组除第 14天组外 ,其余各时间组凋亡指数均明显大于BLM组 ,P <0 .0 5～ 0 .0 1;( 7)凋亡抑制基因Bcl 2的表达在DXM组明显低于BLM组。结论　DXM通过诱导肺内炎症细胞凋亡增加 ,减轻BLM所致

Influence of Dexamethasone on the Proliferation & Apoptosis of Pulmonary Inflammatory Cells in Bleomycin-Induced Pulmonary Fibrosis in Rats

Purpose To study the interfering role of dexamethasone on the state of proliferation/apoptosis of the pulmonary inflammatory cells in rat pulmonary fibrosis models induced by bleomycin. Methods Seventy five pathogen free Sprague Dawley (SD) rats were randomly divided into three groups (25 in each group),they were control(C),bleomycin(BLM) and dexamethasone (DXM) group.Each group was divided again into 5 subgroups (1 ,3 ,7 ,14 and 28 day).The bronchoalveolar lavage fluid (BALF) were gotten and the cells counting as well as differentiation were figured out;the lower DNA content (the sub G1 peaks can reflect low molecular weight[LMW] DNA) in apoptotic cells was detected and quantitated by flow cytometry.HE stain was done to observe the extent of alveolitis and fibrosis of lung tissue;the morphological changes of apoptosis cells were observed by transmissional electron microscope;the semi quantity of apoptosis cells in lung tissue was assayed by in situ TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick endlabeling). Results (1) In DXM group,the total number of inflammatory cells and the percentage of neutrophils in BALF in almost every subgroup were significantly lower than those in related subgroups of BLM ( P <0.01).(2) The percentages of apoptotic cells in BALF in 14 day and 28 day subgroups of DXM were obviously higher than those in related subgroups of BLM ( P <0.05).(3) The peak of alveolitis in DXM shifted backward and the extent of fibrosis was lower than that in BLM.(4) The number of apoptosis cells in DXM was more than that in BLM,and the collagenic fiber in DXM was less than that in BLM under transmissional electron microscope.(5) The apoptosis index(AI) of inflammatory cells in each subgroups of DXM was higher than that in related subgroups of BLM except 14 day.(6) The expression of positive signal of Bcl 2 were more obvious in groups of BLM than that in DXM. Conclusions Dexamethasone can induce apoptosis of pulmonary inflammatory cells and reduce the extent of alveolitis and fibrosis in bleomycin induced pulmonary fibrosis in rats. It suggests that to induce the apoptosis of pulmonary inflammatory cells might be a new way to treat pulmonary fibrosis.