甲苯磺酸瑞马唑仑通过调节CX3CL1-CX3CR1信号通路对老年大鼠肝部分切除术后认知功能障碍的影响  

Effects of remazolam toluene sulfonate on cognitive dysfunction after partial hepatectomy in elderly rats by regulating the CX3CL1-CX3CR1 signaling pathway

作　　者：陈龙平[1] 李军[1] CHEN Longping;LI Jun(Anesthesiology Department,Mianyang Central Hospital,Mianyang 621000,China)

机构地区：[1]绵阳市中心医院麻醉科,621000

出　　处：《免疫学杂志》2024年第12期883-887,共5页Immunological Journal

基　　金：四川省国际医学交流促进会科研课题(L20200509011)。

摘　　要：目的探讨甲苯磺酸瑞马唑仑(RT)对老年大鼠肝部分切除术后认知功能障碍及趋化因子C-X3-C-基元配体1/趋化因子C-X3-C-基元受体1(CX3CL1-CX3CR1)信号通路的影响。方法将所有实验大鼠随机分为对照组(Control组)、模型组(POCD组)、甲苯磺酸瑞马唑仑低、高剂量处理组(RT-L、RT-H组)、甲苯磺酸瑞马唑仑高剂量处理+CX3CL1抗体组(RTH+CX3CL1抗体组),建立肝部分切除老年大鼠模型并按分组给予相应药物处理;Morris水迷宫检测大鼠认知功能;ELISA检测大鼠血清中炎性因子TNF-α、IL-6水平;Nissl染色观察大鼠海马组织神经元病理情况;TUNEL染色检测大鼠神经元细胞凋亡情况;Western blot检测凋亡相关蛋白Bax、Caspase-3、C-caspase-3及CX3CL1-CX3CR1信号通路相关蛋白表达情况。结果给予RT可减少老年POCD大鼠逃避潜伏期,增加大鼠穿越平台次数,减轻神经元损伤,细胞排列基本整齐,细胞增多,核固缩现象减轻,核仁相对清晰,降低TNF-α、IL-6水平和神经元凋亡指数及Bax、Caspase-3、C-caspase-3表达,升高CX3CL1、CX3CR1表达,高剂量处理效果更显著;CX3CL1抗体可部分逆转RT对POCD的改善作用。结论甲苯磺酸瑞马唑仑可改善老年大鼠肝部分切除术后认知功能障碍,其作用机制与激活CX3CL1-CX3CR1信号通路有关。Objective To investigate the effects of remazolam toluene sulfonate(RT)on cognitive dysfunction and chemokine C-X3-C motif ligand 1/chemokine C-X3-C motif receptor 1(CX3CL1-CX3CR1)signaling pathway in elderly rats after partial hepatectomy.Methods All experimental rats were randomly separated into a Control group,a model group(POCD group),a low-dose and high-dose remazolam toluene sulfonate groups(RT-L,RT-H groups),and a high-dose remazolam toluene sulfonate+CX3CL1 antibody group(RT-H+CX3CL1 antibody group).A partial hepatectomy elderly rat model was established and corresponding drug treatments were given according to the groups.Morris water maze was applied to detect cognitive function in rats.ELISA was applied to detect the levels of inflammatory factors TNF-αand IL-6 in rat serum.Nissl staining was applied to observe the pathological changes of hippocampal neurons in rats.TUNEL staining was applied to detect neuronal cell apoptosis in rats.Western blot was applied to detect the expression of apoptosis related proteins Bax,Caspase-3,C-caspase-3,and CX3CL1-CX3CR1 signaling pathway related proteins.Results RT reduced the escape latency of POCD in aged rats,increased the number of rats crossing the platform,alleviated neuronal damage,basically arranged cells,increased cell number,alleviated nuclear pyknosis,relatively clear nucleolus,decreased TNF-α,IL-6 levels,neuronal apoptosis index and Bax,Caspase-3,C-caspase-3 expression.The expression of CX3CL1 and CX3CR1 was increased,and the effect was more significant at high dose.CX3CL1 antibody can partially reverse the improvement of RT on POCD.Conclusion Remazolam toluene sulfonate can improve cognitive function after partial hepatectomy in elderly rats,and its mechanism of action is related to the activation of the CX3CL1-CX3CR1 signaling pathway.

关 键 词：甲苯磺酸瑞马唑仑 趋化因子C-X3-C-基元配体1/趋化因子C-X3-C-基元受体1信号通路 肝部分切除术 术后认知功能障碍 

分 类 号：R741.02[医药卫生—神经病学与精神病学]