CX3CL-1/CX3CR1信号调控的小胶质细胞活化在右美托咪定改善小鼠认知功能中的作用

The role of microglia activation regulated by CX3CL-1/CX3CR1 signal in cognitive function in mice improvedbydexmedetomidine

目的按探究CX3CL-1/CX3CR1信号在右美托咪定(Dex)改善七氟醚诱导老龄小鼠认知功能障碍中的作用。方法野生型(WT)小鼠与CX3CR1敲除(CX3CR1^(-/-))小鼠各30只,各分为对照组,模型组,Dex组,每组10只。取模型组与Dex组小鼠以3%七氟醚麻醉,行肝脏切除术。术后每天腹腔注射20μg·kg^(-1)Dex,连续治疗7d,之后开展水迷宫实验与跳台实验。取小鼠脑组织分别开展苏木精-伊红染色、TUNEL染色、免疫组化染色、树突棘染色、电生理测试、Westernblot实验。丝结果与对照组相比,模型组小鼠水迷宫逃避潜伏期明显增加,穿越平台次数减少,第I象限停留时间减少,跳台错误潜伏期明显减少,跳台错误次数明显增加。在WT小鼠中,Dex明显减少了小鼠逃避潜伏期,增加了穿越平台次数与第I象限停留时间,提高了跳台错误潜伏期,减少了跳台错误次数。但在CX3CR1^(-/-)小鼠中,Dex对小鼠水迷宫测试和跳台实验中行为没有明显影响。此外,与模型组相比,WT小鼠经Dex治疗后,ibal表达明显减少,NLRP3表达降低,神经元状态明显恢复,TUNEL阳性细胞数明显减少。与此同时,Dex治疗明显增加了CX3CL-1/CX3CR1信号表达,提高了小鼠海马区fEPSP斜率,提高了树突棘密度。然而,对于CX3CR1^(-/-)小鼠,Dex对神经炎症,神经元凋亡以及树突棘的损伤没有明显影响。结论Dex通过激活CX3CL-1/CX3CR1信号抑制小胶质细胞活化,从而减轻神经炎症与神经元凋亡,提高树突棘密度,最终改善小鼠认知功能障碍。

ObjectiveTo explore the effect of CX3CL-1/CX3CR1 signaling in the improvement of sevoflurane-induced cognitive dysfunction in aged mice by dexmedetomidine(Dex).Methods 30 wild-type(WT)mice and 30 CX3CR1 knockout(CX3CR1-s)mice were divided into control group,model group,and Dex group,10 mice in each group.Mice in model group and Dex group were anesthetized with 3%sevoflurane and undergo hepatectomy.After surgery,20μg·kg^(-1)Dex i.p.was administrated for continuous 7 days,and then the water maze test and step down test were carried out.Brains were sectioned for HE staining,TUNEL staining,immunohistochemical staining,dendritic spine staining,electrophysiological test,Western blot test.Results Compared with control group,the escape latency in water maze test of mice in model group increased significantly,the number of crossing platforms decreased,the resident time in the first quadrant decreased.In addition,the step down latency significantly reduced,and the error times increased significantly.In WT mice,Dex significantly reduced the escape latency of the mice in water maze test,increased the number of platform crossings and the resident time of the first quadrant,increased the step down latency,and reduced error times.However,in CX3CR1^(-/-)mice,Dex had no significant effect on the behavior of the mice in water maze test and step down test.In addition,