肺微血管内皮细胞表型改变与博莱霉素所致大鼠肺纤维化的关系

Role of ultrastructural and functional changes of lung microvascular endothelial cells in pothogenesis of bleomycin induced lung fibrosis in rat

目的:观察博莱霉素所致肺纤维化大鼠微血管内皮细胞(LMVECs)超微结构及血清CTGF的变化,探讨肺微血管内皮细胞表型及与博莱霉素损伤肺纤维化间的关系.方法:SD大鼠45只,随机分为3组:博莱霉素(BLM)组,肺炎链球菌组及正常对照组,每组15只,分别气管滴注博莱霉素及肺炎链球菌造模,对照组滴注生理盐水.电镜观察外周肺组织内皮细胞超微结构,同时测定血清CTGF含量.结果:光镜及电镜显示肺炎组与BLM组的不同改变.肺炎组组织学及肺微血管内皮细胞超微结构表现为典型的急性炎症损伤修复,之后肺组织结构恢复正常.BLM组表现为肺组织损伤的持续进行,肺微血管内皮细胞7d开始增殖并出现形态学的改变,且贯穿实验各个阶段,最终胶原明显沉积于肺泡间隔.血清CTGF测定:肺炎组3d开始增高,第7d骤降至(5.04±0.82)ng/L,第21d恢复至(12.06±0.43)ng/L.BLM组全程增高,第7d至(12.53±2.36)ng/L,第21d增至高峰(19.45±0.41)ng/L.结论:肺微血管内皮细胞功能的转变及其分泌CTGF时相和量的异常可能是博莱霉素所致肺纤维化发生发展的重要环节.

AIM： To observe the microstructural changes in the lung microvascular endothelial cells（LMVECs） and serum level of connective tissue growth factor（CTGF） in bleomycin induced lung fibrosis and their relationship with the pathogenesis of bleomycin induced lung fibrosis in rat. METHODS ： Forty-five SD rats were randomly divided into 3 groups（ n = 15 in each group） which received administration of bleomycin（ BLM）, Streptococcus pneumonia（SP） suspension and normal saline in the trachea, respectively. The histological changes of the tissues were examined by HE and VG staining. The microstructure of LMVECs was observed under electron microscope. The serum level of CTGF was determined by ELISA. RESULTS： In pneumonia group, the histology of the lung and the microstructure of LMVECs manifested a typical acute inflammatory changes with no permanent damages. In the BLM group, the destruction proceeded progressively. The proliferation and the morphological changes of LMVECs started from the 7^th day and persisted throughout the experiment. Collagen deposition in the septa between the alveoli was evident in the end. The serum CTGF level of the rats challenged with SP reflected a temporary elevation and negative feed-back rebound that started to rise at the 3^rd day and dropped drastically to （5.04 ±0.82） ng/L at the 7^th day then returned to （ 12.06 ± 0.43 ） ng/L after SP challenge. The serum CTGF level of the rats with BLM challenge increased all the way up to （ 12.53 ±2.36） ng/L at 7th day and （ 19.45 ± 0.41 ） ng/L at the 21 st day after BLM challenge. CONCLUSION： The changes of funcition and CTGF contents in LMVECs might contribute to the pathogenesis of bleomycin induced lung fibosis.