[阻塞性肺气肿大鼠模型肺组织中基质金属蛋白酶的表达及支气管肺泡灌洗液中某些细胞因子的水平]

[Expression of matrix metalloproteinases in lung tissue and levels of some cytokines in bronchoalveolar lavage fluid in the obstructive emphysema rat models].

作者信息

An Li, Zhang Hong-yu, Pang Bao-sen, Niu Shu-jie, Ma Li, Xin Ping, Weng Xin-zhi

机构信息

Department of Respiratory Disease, Beijing Chaoyang Hospital, Beijing Institute of Respiratory Medicine, Capital University of Medical Sciences, Beijing 100020, China.

出版信息

Zhonghua Nei Ke Za Zhi. 2003 Mar;42(3):181-5.

PMID:12816701

Abstract

OBJECTIVE

To observe the changes of matrix metalloproteinase-2 (MMP-2), MMP-9 and interleukin-10 (IL-10), tumor necrosis factor-alpha (TNFalpha) in lung tissue of the obstructive emphysema rat models and to evaluate the relationship between these changes and emphysema formation.

METHODS

The rat emphysema models were established by exposure to cigarette smoking. Pulmonary function tests were performed to evaluate the forced expiratory volume in 0.3 second (FEV(0.3)), FEV(0.3)/forced vital capacity (FVC) and functional residual capacity (FRC). The morphological indices of emphysema were measured by computer image analyzer. The protein expression and enzymatic activity of MMPs in lung tissue were observed. The contents of IL-10 and TNFalpha in bronchoalveolar lavage fluid (BALF) were measured.

RESULTS

Pulmonary function test showed that in model group the FEV(0.3)/FVC was decreased, whereas the FRC was increased significantly than those in control group (P < 0.01, respectively). There was a significant decrease in the relative content of elastin in lung tissue in model group than that in control group. The expression and enzymatic activity of MMP-2 and MMP-9 in lung tissue, the counts of total leukocytes and neutrophils and the level of TNFalpha in BALF were significantly elevated, but the level of IL-10 in BALF was significantly reduced in model group compared with those in control group (P < 0.01, respectively). There were statistically significant positive correlations between the enzymatic activity of MMP-2, MMP-9 and the total leukocyte counts (P < 0.01, respectively), and significant negative correlations between the enzymatic activity of MMP-2, MMP-9 and the content of elastin (P < 0.05, respectively).

CONCLUSIONS

MMP-2, MMP-9, IL-10 and TNFalpha may play an important role in the formation of obstructive emphysema in rat models caused by passive smoking.

摘要

目的

观察阻塞性肺气肿大鼠模型肺组织中基质金属蛋白酶-2（MMP-2）、MMP-9、白细胞介素-10（IL-10）及肿瘤坏死因子-α（TNFα）的变化，并评估这些变化与肺气肿形成之间的关系。

方法

通过暴露于香烟烟雾建立大鼠肺气肿模型。进行肺功能测试以评估0.3秒用力呼气量（FEV(0.3)）、FEV(0.3)/用力肺活量（FVC）和功能残气量（FRC）。用计算机图像分析仪测量肺气肿的形态学指标。观察肺组织中基质金属蛋白酶的蛋白表达和酶活性。测量支气管肺泡灌洗液（BALF）中IL-10和TNFα的含量。

结果

肺功能测试显示，模型组的FEV(0.3)/FVC降低，而FRC比对照组显著增加（分别为P < 0.01）。模型组肺组织中弹性蛋白的相对含量比对照组显著降低。与对照组相比，模型组肺组织中MMP-2和MMP-9的表达及酶活性、BALF中总白细胞和中性粒细胞计数以及TNFα水平显著升高，但BALF中IL-10水平显著降低（分别为P < 0.01）。MMP-2、MMP-9的酶活性与总白细胞计数之间存在统计学显著正相关（分别为P < 0.01），MMP-2、MMP-9的酶活性与弹性蛋白含量之间存在显著负相关（分别为P < 0.05）。