细胞因子、明胶酶B在烟雾暴露大鼠慢性阻塞性肺疾病发病中的作用及丹参酮Ⅱ-A干预研究  

Role of cytokine and gelatinase B in pathogenesis of chronic obstructive pulmonary disease of rat caused by smoke exposure and interference study with tanshinone Ⅱ-A

作　　者：霍建民[1] 桑玉兰[1] 陈晶莹[1] 石玉枝[1] 周转转[1] 张亚军[1] 

机构地区：[1]哈尔滨医科大学第一临床医学院呼吸内科,150001

出　　处：《国际呼吸杂志》2007年第4期241-245,共5页International Journal of Respiration

基　　金：黑龙江省自然科学基金资助项目（D200535）

摘　　要：目的观察丹参酮Ⅱ-A磺酸钠（STS）对吸烟引致大鼠慢性阻塞性肺疾病（COPD）的干预效果。方法应用单纯吸烟法引致大鼠COPD模型，雾化吸入STS液进行干预，并设健康和COPD两个对照组，常规进行大鼠支气管肺泡灌洗液（BALF）细胞计数；采用ELISA法测定BALF中明胶酶B既基质金属蛋白酶9（MMP-9）的活性及白介素8（IL-8）和肿瘤坏死因子α（TNF-α）的含量；肺组织切片进行苏木素伊红染色形态学观察，用图像分析系统定量分析肺平均内衬间隔（MLI）、平均肺泡数（MAN）、肺泡腔面积与总面积比（PAA）；采用Weigert弹力纤维染色和弹性蛋白电子染色法及透射电镜分析大鼠肺内弹力纤维的结构和分布，并测量弹力纤维的相对面积。结果COPD对照组BALF中MMP-9的活性及IL-8和TNF-α的含量与BALF中自细胞总数、中性粒细胞百分比、中性粒细胞绝对计数均呈正相关。COPD对照组大鼠肺内弹力纤维受到严重破坏，MLI、PAA比健康对照组增高、MAN和弹力纤维的相对面积低于健康对照组，BALF中MMP-9的活性及IL-8和TNF-α的含量均明显高于健康对照组；而吸入STS组大鼠肺内弹力纤维排列整齐、连续，呈片状、条索状，与胶原纤维伴随，与健康对照组大鼠肺内弹力纤维变化相似，BALF中MMP-9的活性及IL-8和TNF-α的含量、MLI、PAA、MAN和弹力纤维的相对面积均介于COPD组和健康对照组之间。结论单纯吸烟可导致大鼠COPD，气道和肺泡内的MMP-9、IL-8和TNF-α均可能参与了破坏弹力纤维和COPD的形成过程。STS可减轻吸烟对肺弹力纤维的破坏作用，抑制吸烟引起的气道局部炎症，具有一定的防治大鼠实验性COPD的作用。Objective To observe interference effect of sodium tanshinone Ⅱ-A sulonate （STS） in chronic obstructive pulmonary disease（COPD） of rat caused by smoke exposure. Methods Rat model of COPD was established by exposuring Wistar rats to cigarette smoke daily and then had interference with nebulising STS solution. Rats were divided into control group and COPD group. Total cell counts and neutrophil counts in BALF were examined routinely. Activity of gelatinase B matrix metalloproteinase-9 （MMP-9） ,contents of interleukin-8（IL-8） and tumor necrosis factor-α（TNF-α） in BALF were determined with ELISA; Lung tissue section stained by HE was observed for the morphological alternations and mean linear intercept（MLI） ,mean alveolar number（MAN） and proportion of alveolar area（PAA） were measured. The structure and distribution of elastic fibers were analyzed with Weigert elastic fibers stained, with the transmission electronmicroscope and with elastin electron stain. And the percentage of relative area and area of elastic fiber was measured. Results Activity of MMP-9 and contents of IL-8,TNF-α in BALF in COPD rats showed positive correlations to the total counts of white blood cell （WBC）, percentage of neutrophil and the counts of neutrophil in BALF. Pulmonary elastic fibers of rats in COPD group were broken severely,and MLI, PAA were higher than those in control group; MAN and relative area of elastic fibers were lower than those in control group. Activity of MMP-9 and contents of IL-8 ,TNF-α in BALF were obviously higher than those in control group. Pulmonary elastic fibers of rats with nebulising STS were resemble to those in control group： regular, continuous, lamellar, funicular, and accompanied with collagenous fiber. Activity of MMP-9 and contents of IL-8,TNF-α in BALF,MLI, PAA,MAN and the relative area of elastic fibers were between COPD group and control group. Conclusions COPD of rats was caused by cigarette smoking. MMP-9,IL-8 and TNF-α in airway and lung alveoli probably

关 键 词：丹参酮Ⅱ-A 慢性阻塞性肺疾病 吸烟 

分 类 号：R563[医药卫生—呼吸系统]