目的:探讨贝伐珠单抗（bevacizumab，BEV）对缺血性脑卒中损伤的影响及作用机制。 方法:以雄性C57BL/6J小鼠为研究对象，建立大脑中动脉闭塞（middle cerebral artery occlusion，MCAO）模型，将42只C57BL/6J小鼠随机分为3组：假手术（Sham）组、MCAO组、BEV组，每组14只。采用Zea‑Longa评分、TTC染色、H&E染色、尼氏染色、免疫组化、Western blot等方法检测BEV对MCAO小鼠的影响。 结果:与Sham组相比，MCAO组小鼠Zea‑Longa评分及脑梗死体积百分比明显增加（P<0.01）；缺血侧脑组织细胞结构形态破坏及神经元明显损伤，尼氏小体含量减少；VEGF、AKT、PI3K蛋白表达水平和Bcl‑2/Bax、P‑AKT/AKT蛋白比值明显降低（P<0.01）。与MCAO组相比，BEV组小鼠Zea‑Longa评分及脑梗死体积百分比明显增加（P<0.01）；缺血侧脑组织细胞结构形态破坏及神经元损伤更严重，尼氏小体明显减少甚至消失；PI3K蛋白表达水平明显降低（P<0.05），VEGF蛋白表达水平和Bcl‑2/Bax、P‑AKT/AKT蛋白比值进一步明显降低（P<0.05）。 结论:BEV加重缺血性脑卒中小鼠的损伤，其机制可能与VEGF/PI3K/AKT信号通路有关。

Objective:To investigate the effect and mechanism of bevacizumab （BEV） on ischemic stroke injury. Methods:Male C57BL/6J mice were used to establish a middle cerebral artery occlusion （MCAO） model. A total of 42 C57BL/6J mice were randomly assigned into three groups： Sham group， MCAO group， and BEV group， with 14 mice in each group. The effects of BEV on MCAO mice were detected by Zea‑Longa score， TTC staining， H&E staining， Nissl staining， immunohistochemistry， and Western blot. Results:Compared to the Sham group， mice in the MCAO group exhibited increases in the Zea‑Longa score and the percentage of cerebral infarct volume （P<0.01）. The morphological structure of brain tissue cells on the ischemic side was disrupted， with significant neuronal injury and a reduction in Nissl body content. Additionally， there were decreases in the protein expression levels of VEGF， AKT， and PI3K， as well as Bcl‑2/Bax and P‑AKT/AKT protein ratios （P<0.01）. Compared to the MCAO group， mice in the BEV group showed significant increases in the Zea‑Longa score and the percentage of cerebral infarct volume （P<0.01）. The morphological structure of brain tissue cells on the ischemic side was more severely disrupted， with more pronounced neuronal injury and a significant reduction or even disappearance of Nissl bodies. The expression level of PI3K protein was decreased （P<0.05）， and the expression level of VEGF protein， Bcl‑2/Bax and P‑AKT/AKT protein ratios were further significantly reduced （P<0.05）. Conclusion:BEV aggravates the injury in mice with ischemic stroke， and its mechanism may be related to the VEGF/PI3K/AKT signaling pathway.

R743.3

河北省医学科学研究课题计划（20200541）