慢性阻塞性肺疾病大鼠肺内白细胞介素-8和肿瘤坏死因子-α与气道炎症的关系研究

Interleukin-8 and tumor necrosis factor-α are contributing to airw ay inflammation in rat model of chronic obstructive pulmonary disease

目的 探讨白细胞介素 8(IL 8)在慢性阻塞性肺疾病 (COPD)发病机制中的作用。方法单纯熏香烟法建立COPD模型 ,支气管肺泡灌洗计数支气管肺泡灌洗液 (BALF)中细胞计数和百分比 ,酶联免疫吸附法 (ELISA)测定BALF和血清中的IL 8与肿瘤坏死因子 α(TNF α)浓度 ,肺组织切片行苏木素 伊红染色观察形态学改变 ,采用图像分析系统定量测定肺平均内衬间隔 (MLI)、平均肺泡数 (MAN)和肺泡腔面积与总面积比 (PAA)。结果 COPD组MLI、PAA比正常对照组增高 ,而MAN低于对照组 ,差异有统计学意义 (P <0 0 1)。与正常对照组比较 ,COPD组BALF中IL 8浓度 [(114 5±15 7)pg/ml对 (2 59 4± 2 0 1)pg/ml ,P <0 0 1]、TNF α浓度 [(80 5± 9 5)pg/ml对 (14 5 9± 17 3 )pg/ml ,P <0 0 1]、白细胞总数 [(1 64± 0 12 )× 10 8/L对 (5 76± 0 2 9)× 10 8/L ,P <0 0 1]、中性粒细胞绝对计数 [(0 0 99± 0 0 65)× 10 8/L对 (1 2 6± 0 2 5)× 10 8/L ,P <0 0 1]、中性粒细胞百分比 [(5 9± 3 6) %对(2 1 8± 3 7) % ,P <0 0 5]均增高 ,差异有统计学意义。COPD组血清中IL 8浓度亦比对照组增高[(45 2± 13 5)pg/ml对 (85 7± 7 0 )pg/ml ,P <0 0 1]。COPD组BALF中IL 8浓度与BALF中白细胞总数。

Objective To explore the role of interleukin-8(IL-8) in the pathogene sis of COPD MethodsRat model of chronic obstructive pulmonary disease(COPD) was established by exposure Wistar rats to cigarette smoke dai ly for 120 days Total cell counts and neutrophil counts in BALF were examined The levels of IL-8 and tumor necrosis factor-α(TNF-α) in BALF and serum wer e measured with ELISA Lung tissue section stained by HE was observed to study t he morphological alternations and MLI,MAN and PAA were measured Result sMLI and PAA in COPD rat were higher than those in control group (P <0 01) while MAN was decreased on the contrary Statistic analysis showed that levels of IL-8 [(114 5±15 7)pg/ml vs (259 4±20 1)pg/ml,respectiv ely,P<0 01],TNF-α[(80 5±9 5)pg/ml vs(145 9±17 3)pg/ml,P <0 01],total cell counts[(1 64±0 12)×10 8 /L vs (5 76±0 29 )×10 8 /L,P<0 01],neutrophil counts [(0 099±0 065)×10 8 /L vs (1 26±0 25)×10 8 /L,P<0 01],neutrophil proportion[(5 9±3 6)% vs(21 8±3 7)%,P<0 05]in BALF in COPD group were higher than those in the control group The level of IL-8 in serum in COPD group was higher than those of control group [(45 2±13 5)pg/ml vs (85 7±7 0)pg/ml ,P<0 01] Positive correlations were demonstrated between the level of IL-8 or the level of TNF-α and neutrophil counts in BALF in COPD group,but n ot the level of IL-8 or TNF-α in serum ConclusionsOur data implied a close correlation between IL-8 in BALF and airway inflammation in CO PD rat model IL-8 may contribute to the development of COPD through recruitmen t and activation of neutrophil into airways TNF-α may up-regulate the produc tion and release of IL-8 Thus,the synergy of IL-8 and TNF-α may be respons ible for the persistence and amplification of airway inflammation in COPD