Li Li, Ruan Ying-mao, Meng Ying, Chen Ying
Department of Pathology, Fu Wai Hospital, CAMS and PUMC, Beijing 100037, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2004 Jun;26(3):279-84.
To investigate the protective and therapeutic effects of pulmonary surfactant in the pathogenesis of chronic obstructive pulmonary disease (COPD) in hamsters.
COPD animal model was established by smoke inhalations and intratracheal instillations of pancreatic elastase in hamsters. Ninty hamsters were divided into 9 groups as follows: normal group (N), two groups received smoke inhalations for 1 and 3 months (S1 and S3), one group received intratracheal instillation of surfactant (10 mg/100 g BW) for once after 1 month smoking (SP1), one group was treated with surfactant after 1.5, 2 and 2.5 months of smoking (SP3), and two groups received intratracheal administration of elastase (40 U/100 g BW) and were killed after 1 month and 3 months, respectively (E1 and E3). The surfactant was injected intratracheally after 1 week, 0.5, 1.0, 1.5, 2.0, and 2.5 months, followed by administration with elastase (EP1 and EP3). EP1 group were killed at the first month, and EP3 at the third month. Light microscopy and electromicroscopy observations were performed in each group. Pulmonary mean linear intercept (MLI), mean alveolar numbers (MAN), and pulmonary alveolar area (PAA) was measured by image analysis. The expression of surfactant protein A (SP-A) were observed by immunohistochemistry.
Smoking for 3 months and instillations of elastase resulted in chronic bronchitis and emphysema. MLI and PAA increased and MAN decreased in all the experimental groups compared with in the normal group (P < 0.05 or P < 0.01). Administration of surfactant for 3 months resulted in statistically significant inhibition of pulmonary injury. MLI and PAA decreased and MAN increased in SP3 compared with in S3. Only MLI decreased in EP3 compared with E3. The expressions of SP-A in the type II alveolar epithelia decreased in S3 and E3 (compared with the normal group P < 0.01). After pulmonary surfactant intervention, the expression of SP-A increased significantly.
Pulmonary surfactant may have a long-term protective effect on chronic smoking and elastase-induced COPD.
探讨肺表面活性物质对仓鼠慢性阻塞性肺疾病(COPD)发病机制的保护和治疗作用。
通过仓鼠吸入烟雾和气管内滴注胰弹性蛋白酶建立COPD动物模型。90只仓鼠分为9组:正常组(N),两组分别吸入烟雾1个月和3个月(S1和S3),一组在吸烟1个月后气管内滴注一次表面活性物质(10mg/100g体重)(SP1),一组在吸烟1.5、2和2.5个月后用表面活性物质治疗(SP3),两组气管内给予弹性蛋白酶(40U/100g体重),分别在1个月和3个月后处死(E1和E3)。在1周、0.5、1.0、1.5、2.0和2.5个月后气管内注射表面活性物质,随后给予弹性蛋白酶(EP1和EP3)。EP1组在第1个月处死,EP3组在第3个月处死。对每组进行光镜和电镜观察。通过图像分析测量肺平均线性截距(MLI)、平均肺泡数(MAN)和肺泡面积(PAA)。通过免疫组织化学观察表面活性物质蛋白A(SP-A)的表达。
吸烟3个月和滴注弹性蛋白酶导致慢性支气管炎和肺气肿。与正常组相比,所有实验组的MLI和PAA增加,MAN减少(P<0.05或P<0.01)。给予表面活性物质3个月导致对肺损伤有统计学意义的抑制。与S3组相比,SP3组的MLI和PAA降低,MAN增加。与E3组相比,EP3组仅MLI降低。S3组和E3组II型肺泡上皮细胞中SP-A的表达降低(与正常组相比P<0.01)。肺表面活性物质干预后SP-A的表达显著增加。
肺表面活性物质可能对慢性吸烟和弹性蛋白酶诱导的COPD有长期保护作用。