目的：探讨利拉鲁肽（Liraglutide）对糖尿病合并脑缺血损伤大鼠的神经保护作用及其可能的机制。 方法：SD大鼠36只随机分为3组：假手术组（Sham组）、糖尿病大脑中动脉缺血组（DM+MCAO组）和利拉 鲁肽干预组（Liraglutide组）。糖尿病模型造模完成后1周，各组给予相应干预1周，再进行MCAO模型造 模。MCAO造模24 h后进行神经功能缺损评分，TTC染色法进行脑梗死体积测定，Western Blotting法检测 Toll 样受体 4（TLR4）和髓样分化因子 88（Myd88）蛋白的表达，荧光实时定量 PCR 法检测核转录因子κB （NF-κB）p65 mRNA的转录水平，ELISA法检测炎症因子白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α的浓 度。结果：DM+MCAO组和Liraglutide组注射链脲佐菌素1周后血糖显著升高（P＜0.05），Liraglutide组注 射利拉鲁肽干预1周后血糖显著降低（P＜0.05）。与DM+MCAO组相比，Liraglutide组神经功能缺损评分 显著下降（P＜0.05）、脑梗死体积显著降低（P＜0.05）、TLR4和Myd88蛋白表达显著降低（P＜0.05）、NF-κB p65 mRNA转录水平显著下降（P＜0.05）, IL-1β和TNF-α的水平显著降低（P＜0.05）。结论：利拉鲁肽对糖 尿病合并脑缺血损伤有神经保护作用，其机制可能通过抑制TLR4/Myd88信号通路介导的炎症反应。

To explore the neuroprotective effects and potential mechanism of liraglutide on diabetic rats with ischemic brain injury. Methods: A total of 36 rats were randomly divided into the sham operation group (Sham group), diabetes mellitus and middle cerebral artery occlusion group (DM+MCAO group), and liraglutide treatment group (Liraglutide group). One week after establishing the diabetes mellitus model, each group was given its corresponding treatment for 1 week, and a cerebral ischemia (MCAO) model was then created. Twenty-four hours after development of the MCAO model, neurological behavior was evaluated by neurological deficit scores; infarct volume was analyzed with TTC staining; expression of TLR4 and Myd88 proteins was measured by Western Blotting; expression of NF-κB p65 mRNA was detected by real-time PCR; and concentrations of IL-1β and TNF-α were measured by ELISA. Results: Blood glucose of the DM+MCAO and Liraglutide groups significantly increased 1 week after injection of STZ (P<0.05), and blood glucose of the Liraglutide group significantly decreased 1 week after injection of liraglutide (P<0.05). Compared with that of the DM+MCAO group, the neurological deficit scores and infarct volume of the Liraglutide group significantly declined (P<0.05), protein expression of TLR4 and Myd88 significantly decreased (P<0.05), mRNA expression of NF-κB p65 significantly decreased (P<0.05), and concentrations of IL-1β and TNF-α significantly decreased (P< 0.05). Conclusion: Our data indicate that the liraglutide exerts neuroprotective effects on diabetic rats with ischemic brain injury possibly through inhibiting the inflammatory response mediated by the TLR4/Myd88 signal pathway.