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伊马替尼减轻大鼠蛛网膜下腔出血后早期脑损伤的作用研究

Effect of imatinib on alleviating early brain injury after subarachnoid hemorrhage in rats
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摘要 目的 探讨伊马替尼对大鼠蛛网膜下腔出血(SAH)后早期脑损伤(EBI)的影响及其可能的作用机制。方法 采用颈内动脉穿刺法构建SAH模型,Sprague-Dawley雄性大鼠分为假手术组、模型组和伊马替尼给药组。SAH模型制作30 min后,腹腔注射一次给予伊马替尼50 mg/kg。24 h后对出血情况,神经功能评分,平衡木评分,脑水肿和伊文思蓝渗出进行考察;Western blot考察过氧化物酶体增殖物激活受体γ(PPARγ),Toll样受体4(TLR4),白细胞介素-1β(IL-1β)和肿瘤坏死因子α(TNF-α)的表达量;TUNEL染色考察凋亡的情况。结果 实验结果表明伊马替尼能够显著减轻SAH后的神经损伤和脑损伤。在SAH大鼠模型中,伊马替尼给药显著增加PPARγ表达,抑制TLR4及炎症因子TNF-α,IL-1β的表达从而抑制细胞凋亡的发生。结论 伊马替尼能够激活PPARγ,从而抑制炎症反应减轻SAH后的EBI。 Objective To explore the effect of imatinib on early brain injury(EBI) after subarachnoid hemorrhage(SAH) in rats. Methods The SAH model was established by internal carotid artery puncture. Sprague-Dawley male rats were divided into sham operation group, model group and imatinib administration group. After the SAH model was made for 30 minutes 50 mg/kg of imatinib was given by intraperitoneal injection. After 24 hours, hemorrhage, neurological function score, balance beam score, cerebral edema and Evans blue exudation were investigated. Western blot examined the peroxisome proliferator activated receptors γ(PPARγ), toll-like receptor 4(TLR4), interleukin-1 beta(IL-1β) and tumor necrosis factor(TNF-α). TUNEL staining was used to investigate apoptosis. Results The results showed that imatinib can significantly reduce nerve injury and brain injury after SAH. In the SAH rat model, imatinib administration significantly increased the expression of PPARγ and inhibited the expressions of TLR4 and inflammatory factors TNF-α and IL-1β, thereby inhibiting the occurrence of apoptosis. Conclusion Imatinib can activate PPARγ to inhibit inflammatory reaction and alleviate EBI after SAH.
作者 韩雨薇 王晨辰 梁国标 李晓明 HAN Yu-wei;WANG Chen-chen;LIANG Guo-biao;LI Xiao-ming(Department of Neurosurgery,General Hospital of Northern Theater Command,Shenyang 110016,China)
出处 《临床神经外科杂志》 2023年第1期57-61,共5页 Journal of Clinical Neurosurgery
基金 国家自然科学基金面上项目(81971133) 沈阳市科技计划项目(20-205-4-098) 中国博士后面上基金(2020M673679)。
关键词 伊马替尼 蛛网膜下腔出血 PPARΓ 炎症 imatinib subarachnoid hemorrhage PPARγ inflammation
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