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博来霉素诱导的肺纤维化与血管内皮细胞损伤之间的关系

[Relationship between bleomycin-induced pulmonary fibrosis and vascular endothelial cell injury].

作者信息

Wei Jing-guo, Cui Guang-bin, Wang Wei, Wei Long-xiao, Liang Guo-min, Song Li-jun, Xu Jia-kuan

机构信息

Department of Radiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, China.

出版信息

Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2004 Oct;22(5):354-7.

Abstract

OBJECTIVE

To explore the relationship between the injury of vascular endothelial cells and formation of lung fibrosis by bleomycin (BLM) in rats.

METHODS

The rats of experimental groups were treated with bleomycin intratracheally to induce pulmonary fibrosis. The expression of vascular endothelial growth factor (VEGF) in pulmonary tissues were analyzed qualitatively and quantitatively by immunohistochemistry and image analysis system.

RESULTS

(1) HISTOLOGY: Edema in rat alveoli and alveolar septum, inflammatory cells exudation, degeneration and necrosis of type I and type II alveolar epithelial cells (AETI and AETII), ruptured alveolar basement membrane, as well as swollen vascular endothelial cells and karyopyknosis were observed in 3 d and 7 d after treatment with BLM. AETII proliferation, with more fibroblasts in alveolar septum, and new capillary vessel formation in 7, 14 d, as well as thickened alveolar septum, damaged alveolar structure, and obvious pulmonary tissue fibrosis in 28 d after treatment with BLM were observed. (2) Immunohistochemistry: in normal control, VEGF expressed weakly in pulmonary tissue distributing mainly in AETII, bronchial epithelial cells, alveolar macrophages and leydig's cells. While in bleomycin treated groups, the expression of VEGF increased markedly. The expression in AETII, and pulmonary macrophage were significantly higher than that in control in 3 d to 28 d (P < 0.05, P < 0.01). The rat leydig's cells also had higher expression of VEGF in 7, 14, 28 d (P < 0.05, P < 0.01).

CONCLUSION

The high expression of VEGF is related to vascular endothelial cells injury which may be one of important factors in the formation of bleomycin-induced pulmonary fibrosis.

摘要

目的

探讨博来霉素(BLM)致大鼠肺纤维化过程中血管内皮细胞损伤与肺纤维化形成的关系。

方法

实验组大鼠经气管内注入博来霉素诱导肺纤维化。采用免疫组织化学及图像分析系统对肺组织中血管内皮生长因子(VEGF)的表达进行定性及定量分析。

结果

(1)组织学:BLM处理后3天及7天,可见大鼠肺泡及肺泡间隔水肿,炎性细胞渗出,Ⅰ型和Ⅱ型肺泡上皮细胞(AETI和AETII)变性、坏死,肺泡基底膜破裂,血管内皮细胞肿胀、核固缩。BLM处理后7天、14天可见AETII增殖,肺泡间隔成纤维细胞增多,有新的毛细血管形成,28天可见肺泡间隔增厚,肺泡结构破坏,肺组织纤维化明显。(2)免疫组织化学:正常对照组肺组织中VEGF表达较弱,主要分布于AETII、支气管上皮细胞、肺泡巨噬细胞及睾丸间质细胞。而博来霉素处理组VEGF表达明显增加。3天至28天AETII及肺巨噬细胞中的表达明显高于对照组(P<0.05,P<0.01)。7天、14天、28天大鼠睾丸间质细胞中VEGF表达也较高(P<0.05,P<0.01)。

结论

VEGF高表达与血管内皮细胞损伤有关,可能是博来霉素诱导肺纤维化形成的重要因素之一。

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