贝伐珠单抗改善博来霉素诱导的小鼠肺纤维化  

Bevacizumab ameliorates bleomycin-induced murine pulmonary fibrosis

作　　者：黄超文 赵强 钟莲娣 先俊 钟雪莺[1] 仝金斋[1] 黄炎明[1] HUANG Chaowen;ZHAO Qiang;ZHONG Lianti;XIAN Jun;ZHONG Xueying;TONG Jinzhai;HUANG Yanming(Department of Respiratory Medicine,Jiangmen Central Hospital,Jiangmen 529000,China)

机构地区：[1]江门市中心医院呼吸内科一区

出　　处：《实用医学杂志》2019年第15期2379-2383,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金青年基金项目(编号:81700031)

摘　　要：目的利用1,25(OH)2D3(VD)作为对照,探讨血管内皮生长因子(vascular endothelialgrowth factor,VEGF)单抗-贝伐珠单抗(Bevacizumab,Bev)对博来霉素(Bleomycin,Blm)诱导的肺纤维化小鼠模型的影响。方法将C57B/L小鼠随机分为4组。单次气管内注射生理盐水(Con组)或Blm(3 U/kg)(Blm组)构建小鼠肺纤维化模型,造模后滴鼻给予贝伐珠单抗5 mg/(kg·d)(Blm+Bev组)或腹腔内注射VD5μg/(kg·d)(Blm+VD组),对照组给予生理盐水(Con组)。观察小鼠肺组织病理及α-SMA表达变化,检测肺组织胶原及肺泡灌洗液(broncho-alveolar lavage fluid,BALF)中VEGF-A、IL-4、TNF-α含量。结果 Blm组小鼠的肺支气管BALF中VEGF-A升高,并表现出典型肺纤维化病理改变,胶原纤维含量及α-SMA表达显著上升,BALF中IL-4、TNF-α含量明显升高。贝伐珠单抗和VD可减少VEGF-A表达,改善肺部结构破坏、胶原沉积,并降低BALF中IL-4、TNF-α含量。结论贝伐珠单抗可改善Blm诱导的小鼠肺部纤维化及炎症反应。Objective To investigate the role of bevacizumab(Bev)in bleomycin(Blm)-induced pulmonary fibrosis,with 1,25(OH)2D3 as the comparative antifibrotic agent. Methods This study involved 4 groups of C57BL/6 mice.Establishment of pulmonary fibrosis model in mice by single intratracheal injection of saline(Con group)or Blm(3 U/kg)(Blm group),those in Blm + Bev group and Blm + VD group respectively received intranasal administration of Bevacizumab and intraperitoneal injection of VD for 21 days. Pathological changes of the lung,expression of α-SMA,hydroxyproline content,VEGF-A,TNF-α and IL-4 in broncho-alveolar lavage fluid(BALF)were evaluated. Results VEGF-A in BALF was elevated in Blm group in contrast to the Con group. Mice in Blm group showed typical fibrotic pathological changes,severe collagen deposition and increase of α-SMA and TNF-α,IL-4. In addition to suppression of VEGF-A expression in BALF,administration of both bevacizumab and VD attenuated disruption of normal lung architecture and collagen deposition and reduced secretion of TNF-α and IL-4 in BALF. Conclusion Bevacizumab exhibits antifibrotic effect in bleomycin-induced pulmonary fibrosis and regulates inflammation.

关 键 词：血管内皮生长因子 贝伐珠单抗 1 25(OH)2D3 肺纤维化 博来霉素 

分 类 号：R563[医药卫生—呼吸系统]