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沙丁胺醇对大鼠气囊炎症模型中炎症参数和血管生成的影响。

Effects of salbutamol on the inflammatory parameters and angiogenesis in the rat air pouch model of inflammation.

作者信息

Eteraf-Oskouei Tahereh, Akbarzadeh-Atashkhosrow Arezu, Maghsudi Milad, Najafi Moslem

机构信息

Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, I.R. Iran.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, I.R. Iran.

出版信息

Res Pharm Sci. 2017 Oct;12(5):364-372. doi: 10.4103/1735-5362.213981.

Abstract

In the present study, effects of salbutamol on the inflammatory parameters, angiogenesis, interleukin-1 beta (IL-1β) and vascular endothelial growth factor (VEGF) levels were investigated in an air pouch model of inflammation. Inflammation was induced by intrapouch administration of 1% solution of sterile carrageenan in male Wistar rats. Salbutamol (125, 250 and 500 µg/rat) and salbutamol (500 µg/rat) plus propranolol (100 μg/rat) were injected intrapouch. After 6 and 72 h, fluid inside the pouches was collected to measure volume of exudates, leukocytes number and IL-1β levels. To determine angiogenesis, the granulation tissues were dissected out and weighed 3 days after carrageenan injection, then hemoglobin concentration was assessed using a hemoglobin assay kit. In addition, amount of VEGF in the exudates was measured 72 h after induction of inflammation. Leukocyte accumulation and the volume of exudates were significantly inhibited by salbutamol administration. In addition, salbutamol decreased the production of VEGF and IL-1β. Moreover, all used doses of salbutamol significantly inhibited angiogenesis. Interestingly, effects of salbutamol on the attenuation of angiogenesis and inflammatory parameters was similar to diclofenac sodium. Co-administration of propranolol with salbutamol clearly reversed anti-inflammatory effects of salbutamol. Salbutamol can decrease acute and chronic inflammation by β-adrenergic receptors activation. The observed IL-1β and VEGF inhibitory properties of salbutamol may be responsible for anti-inflammatory and anti-angiogenic effect of the agent.

摘要

在本研究中,在炎症气袋模型中研究了沙丁胺醇对炎症参数、血管生成、白细胞介素-1β(IL-1β)和血管内皮生长因子(VEGF)水平的影响。通过向雄性Wistar大鼠气袋内注射1%无菌角叉菜胶溶液诱导炎症。将沙丁胺醇(125、250和500μg/只大鼠)以及沙丁胺醇(500μg/只大鼠)加普萘洛尔(100μg/只大鼠)注入气袋内。6小时和72小时后,收集气袋内的液体以测量渗出液体积、白细胞数量和IL-1β水平。为了确定血管生成情况,在注射角叉菜胶3天后取出肉芽组织并称重,然后使用血红蛋白检测试剂盒评估血红蛋白浓度。此外,在炎症诱导72小时后测量渗出液中VEGF的含量。给予沙丁胺醇可显著抑制白细胞聚集和渗出液体积。此外,沙丁胺醇可降低VEGF和IL-1β的产生。而且,所有使用剂量的沙丁胺醇均显著抑制血管生成。有趣的是,沙丁胺醇对血管生成和炎症参数的减轻作用与双氯芬酸钠相似。普萘洛尔与沙丁胺醇联合给药明显逆转了沙丁胺醇的抗炎作用。沙丁胺醇可通过激活β-肾上腺素能受体来减轻急性和慢性炎症。观察到的沙丁胺醇对IL-1β和VEGF的抑制特性可能是该药物抗炎和抗血管生成作用的原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b125/5615866/99144c896dad/RPS-12-364-g002.jpg

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