【摘要】 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。更多还原

【Abstract】 Objective: 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.更多还原