Bolandi Seyed Mohammadreza, Abdolmaleki Zohreh, Assarehzadegan Mohammad-Ali
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.
Inflammation. 2021 Dec;44(6):2463-2475. doi: 10.1007/s10753-021-01516-w. Epub 2021 Aug 21.
Studies on the bronchial vascular bed have revealed that the number of blood vessels in the lamina propria and under the mucosa of the lung tissue increases in patients suffering from mild to severe asthma. Thus, in this study, a new strategy was employed in respiratory system disorders by angiogenesis inhibition in an ovalbumin (OVA)-induced rat model of asthma. Twenty-one male Wistar albino rats, 8 weeks old, were randomly divided into three groups (n = 7 in each group), including (1) control group, (2) OVA-treated group, and (3) OVA + Bmab (bevacizumab drug). On days 1 and 8, 1 mg of OVA and aluminum hydroxide in sterile phosphate-buffered saline (PBS) were intraperitoneally injected to rats in groups 2 and 3. The control group was only subject to intraperitoneal injection of saline on days 1 and 8. One week after the last injection, the rats (groups 2 and 3) were exposed to OVA inhalation for 30 min at 2-day intervals from days 15 to 25. After sensitization and challenge with OVA, the OVA + Bmab group (group 3) were treated with a 5 mg/kg bevacizumab drug. Genes and protein expression of IL-1β and TNF-α and the expression of vascular endothelial growth factor (VEGF) protein were assessed by real-time PCR and immunohistochemistry respectively, in lung tissue. OVA exposure increased mucosal secretion and inflammatory cell populations in lung tissue and OVA-specific IgE level in serum. Also, VEGF and cytokine factor expression were significantly elevated in the OVA-induced asthma model (p ≤ 0.05). However, rats in OVA + Bmab group showed significantly a decrease in VEGF and IL-1β and TNF-α genes as well as proteins (p ≤ 0.05). The results showed that bevacizumab efficiently diminished bronchial inflammation via downregulation of VEGF expression, followed by inflammatory cells population and cytokines reduction. Angiogenesis inhibition in rats with induced asthma not only suppresses the inflammatory process through blocking VEGF expression but also inhibits the development of new blood vessels and progressing asthmatic attacks.
对支气管血管床的研究表明，从轻度到重度哮喘患者的肺组织固有层和黏膜下的血管数量会增加。因此，在本研究中，通过在卵清蛋白（OVA）诱导的大鼠哮喘模型中抑制血管生成，在呼吸系统疾病中采用了一种新策略。将21只8周龄的雄性Wistar白化大鼠随机分为三组（每组n = 7），包括（1）对照组，（2）OVA处理组，和（3）OVA + Bmab（贝伐单抗药物）组。在第1天和第8天，将1mg OVA和氢氧化铝溶于无菌磷酸盐缓冲盐水（PBS）中，腹腔注射给第2组和第3组的大鼠。对照组在第1天和第8天仅接受腹腔注射生理盐水。最后一次注射一周后，第2组和第3组的大鼠从第15天到第25天每隔2天暴露于OVA吸入30分钟。在用OVA致敏和激发后，OVA + Bmab组（第3组）用5mg/kg贝伐单抗药物治疗。分别通过实时PCR和免疫组织化学评估肺组织中IL-1β和TNF-α的基因和蛋白表达以及血管内皮生长因子（VEGF）蛋白的表达。OVA暴露增加了肺组织中的黏膜分泌和炎症细胞数量以及血清中的OVA特异性IgE水平。此外，在OVA诱导的哮喘模型中，VEGF和细胞因子表达显著升高（p≤0.05）。然而，OVA + Bmab组的大鼠VEGF、IL-1β和TNF-α基因以及蛋白显著降低（p≤0.05）。结果表明，贝伐单抗通过下调VEGF表达，继而减少炎症细胞数量和细胞因子，有效减轻了支气管炎症。在诱导性哮喘大鼠中抑制血管生成不仅通过阻断VEGF表达抑制炎症过程，还抑制新血管的形成和哮喘发作的进展。
