右美托咪定减轻丙泊酚诱导的新生大鼠神经损伤  

Dexmedetomidine alleviates nerve injury induced by propofol in neonatal rats

作　　者：张芳龄 张湲钫 张立 ZHANG Fangling;ZHANG Yuanfang;ZHANG Li(Department of Anesthesiology,Tuberculosis Prevention and Treatment Hospital of Shaanxi Province,Xi′an 710000,China;Department of Comprehensive Surgery,Tuberculosis Prevention and Treatment Hospital of Shaanxi Province,Xi′an 710000,China)

机构地区：[1]陕西省结核病防治院麻醉科,陕西西安710000 [2]陕西省结核病防治院综合外科,陕西西安710000

出　　处：《基础医学与临床》2025年第5期644-650,共7页Basic and Clinical Medicine

基　　金：陕西省卫生健康科研基金(2021D027)。

摘　　要：目的探讨右美托咪定(Dex)对丙泊酚诱导的新生大鼠神经损伤的影响。方法将大鼠分为对照组(control)、腹腔注入丙泊酚构建神经损伤损伤模型组(model,50 mg/kg)、右美托咪定低、中和高剂量干预模型组(Dex-L、Dex-M和Dex-H,分别股静脉注入0.25、0.5和1μg/kg Dex)、以及Dex-H+anti-BDNF(100μg/kg)组,每组12只。检测大鼠神经功能缺陷评分、跳台错误次数、脑指数变化;HE染色检测海马CA1区病理;ELISA检测海马CA1区中白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)水平;TUNEL染色检测海马CA1区神经元凋亡;Western blot检测海马CA1区裂解的天冬氨酸特异性半胱氨酸蛋白酶-3(cleaved caspase-3)、BDNF前体(proBDNF)、成熟型脑源性神经营养因子(mBDNF)、磷酸化酪氨酸激酶B(p-TrkB)、磷酸化磷脂酰肌醇3激酶(p-PI3K)蛋白水平。结果与模型组比较,Dex-L组、Dex-M组、Dex-H组大鼠神经元损伤有所改善,神经功能缺陷评分、跳台错误次数、脑指数、海马CA1区中IL-6、MCP-1、TNF-α水平、神经元凋亡率及cleaved caspase-3、proBDNF蛋白降低,海马CA1区中mBDNF、p-TrkB、p-PI3K蛋白升高(P<0.05);Anti-BDNF减轻了1μg/kg Dex预处理对丙泊酚诱导的新生大鼠神经损伤的影响。结论Dex预处理抑制神经炎性反应、神经元凋亡进而减轻丙泊酚诱导的新生大鼠神经损伤的机制可能与激活mBDNF/TrkB/PI3K通路有关。Objective To investigate the effect of dexmedetomidine(Dex)on propofol-induced nerve injury in neonatal rats.Methods The rats were divided into control group,intra-peritoneally injected propofol to construct nerve injury model group(50 mg/kg),Low,medium and high dose dexmedetomidine intervention model groups(Dex-L,Dex-M and Dex-H with femoral vein injection of 0.25,0.5 and 1μg/kg Dex,respectively),and Dex-H+anti-BDNF(100μg/kg)group,with 12 animals in each group.The neurological deficit score,number of platform jumping errors,and changes in brain index were detected in rats.HE staining microscopy was applied to measure pathology in the hippocampal CA1 region.ELISA was applied to detect level of interleukin-6(IL-6),monocyte chemotactic protein-1(MCP-1)and tumor necrosis factor-α(TNF-α)in the hippocampal CA1 region.TUNEL staining microscopy was used to measure neuronal apoptosis in the hippocampal CA1 region.Western blot was applied to measure the cleaved caspase-3,proBDNF,mature brain-derived neurotrophic factor(mBDNF),phosphorylated tyrosine kinase B(p-TrkB),and phosphorylated phosphatidylinositol 3 kinase(p-PI3K)proteins in the hippocampal CA1 region.Results Compared with model group,the neuronal damage in rats was improved in Dex-L group,Dex-M group,and Dex-H group,the neurological deficit score,number of platform jumping errors,brain index,level of IL-6,MCP-1,TNF-αin hippocampal CA1 region,neuronal apoptosis rate,and level of cleaved caspase-3 and pro BDNF proteins all reduced,mBDNF,p-TrkB,and p-PI3K proteins in the hippocampal CA1 region raised(P<0.05).Anti-BDNF inhibited the effect of 1μg/kg Dex pretreatment on propofol induced nerve injury in neonatal rats.Conclusions Dex pretreatment inhibits neuro-inflammation and neuronal apoptosis,thereby reduces propofol induced nerve injury in neonatal rats.Its mechanism may be related to the activation of the mBDNF/TrkB/PI3K pathway.

关 键 词：右美托咪定 神经炎性反应 神经元凋亡 丙泊酚 神经损伤 

分 类 号：R614[医药卫生—麻醉学]