Department of Pharmacology, Karaj Branch, Islamic Azad University, Karaj, Iran.
Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
Inflammopharmacology. 2021 Jun;29(3):683-694. doi: 10.1007/s10787-021-00798-8. Epub 2021 Mar 19.
Bevacizumab with anti-angiogenesis properties reduces the vascular endothelial growth factor (VEGF) level and has widely been used to treat various diseases such as lung diseases and chronic obstructive pulmonary disease (COPD). This study, therefore, aimed to consider the effects of bevacizumab on VEGF receptor 2 (VEGFR2) and lung inflammation of the ovalbumin-induced rat model of airway hypersensitivity.
Twenty-one male Wistar rats were randomly divided into 3 groups (n = 7 in each group): (1) control, (2) ovalbumin (OVA)-sensitized, and (3) OVA-sensitized with bevacizumab (OVA + Bmab). Groups 2 and 3 were sensitized with ovalbumin (OVA) and aluminum hydroxide on days 1, 8 and challenged with OVA on day 15 by atomization for 10 days (inhalation). After OVA sensitization, the OVA + Bmab was treated with bevacizumab for 2 weeks. VEGFR2 was semiquantitatively analyzed in the lungs by immunohistochemistry. VEGF was measured in the lung tissue by ELISA method. The mRNA of IL-10 and IL-6 lung tissue were measured by real-time PCR.
Ovalbumin exposure promoted the expression of VEGF and resulted in inflammatory factors overexpression (p ≤ 0.05). However, rats in OVA + Bmab group showed significantly a decrease in VEGFR2 and IL-1β, IL-6, TNFα, and an increase in IL-10 (p ≤ 0.05).
The results show that bevacizumab efficiently diminishes bronchial inflammation via reducing the expression of VEGFR2, and IL-6 genes and enhancing the expression of IL-10 gene. Hence, bevacizumab could be considered as a potential candidate drug to control pathological conditions relevant to airway hypersensitivity.
具有抗血管生成特性的贝伐珠单抗可降低血管内皮生长因子 (VEGF) 水平，并已广泛用于治疗各种疾病，如肺部疾病和慢性阻塞性肺疾病 (COPD)。因此，本研究旨在探讨贝伐珠单抗对卵清蛋白诱导的气道高反应性大鼠模型中 VEGF 受体 2 (VEGFR2) 和肺炎症的影响。
将 21 只雄性 Wistar 大鼠随机分为 3 组（每组 n=7）：（1）对照组；（2）卵清蛋白 (OVA) 致敏组；（3）OVA 致敏加贝伐珠单抗组 (OVA+Bmab 组)。第 2 组和第 3 组于第 1、8 天用卵清蛋白 (OVA) 和氢氧化铝致敏，第 15 天通过雾化吸入 OVA 10 天（吸入）进行致敏。OVA 致敏后，OVA+Bmab 组用贝伐珠单抗治疗 2 周。通过免疫组织化学法半定量分析肺中 VEGFR2 的表达。采用 ELISA 法检测肺组织中 VEGF 的含量。采用实时 PCR 法检测肺组织中 IL-10 和 IL-6 的 mRNA 表达。
OVA 暴露促进了 VEGF 的表达，并导致炎症因子的过度表达（p≤0.05）。然而，OVA+Bmab 组大鼠的 VEGFR2 及 IL-1β、IL-6、TNFα表达明显降低，IL-10 表达明显升高（p≤0.05）。
研究结果表明，贝伐珠单抗通过降低 VEGFR2 和 IL-6 基因的表达，增强 IL-10 基因的表达，有效减轻支气管炎症。因此，贝伐珠单抗可作为控制气道高反应相关病理状态的潜在候选药物。
