目的 觀察右美托咪定通過調(diào)節(jié)CX3CL1-CX3CR1信號通路對老年大鼠肝部分切除術(shù)術(shù)后認(rèn)知功能障礙（POCD）的改善作用。方法 60只SPF級老年SD大鼠隨機(jī)分為假手術(shù)組、模型組、陽性對照組、右美托咪定組和CX3CL1抗體+右美托咪定組。陽性對照組大鼠于術(shù)前3 d給予布洛芬混懸液35 mg/kg，ig給藥，8 h/次，連續(xù)3 d；除假手術(shù)組外，各組大鼠均實施肝部分切除術(shù)，右美托咪定組和CX3CL1抗體+右美托咪定組術(shù)前30 min均以40 μg/kg右美托咪定ip給藥，假手術(shù)組、模型組及陽性對照組予以ip等劑量生理鹽水。肝臟切除后，CX3CL1抗體+右美托咪定組側(cè)腦室立體定位注射CX3CL1中和抗體1 pmol，單次給藥。新異臂探索實驗評價各組大鼠認(rèn)知功能；Nissl染色觀察各組大鼠海馬組織神經(jīng)元細(xì)胞損傷；ELISA法檢測各組大鼠海馬組織腫瘤壞死因子α（TNF-α）、白細(xì)胞介素6（IL-6）水平；qRT-PCR及Western blotting檢測海馬區(qū)CX3CL1、CX3CR1 mRNA及蛋白的表達(dá)。結(jié)果 與假手術(shù)組比較，模型組大鼠新異臂移動距離與停留時間占比下降，神經(jīng)元細(xì)胞存活數(shù)量減少，海馬神經(jīng)元細(xì)胞損傷，海馬組織炎癥因子水平升高，海馬區(qū)CX3CL1、CX3CR1 mRNA及蛋白相對表達(dá)量降低（P<0.05），經(jīng)右美托咪定干預(yù)后POCD大鼠新異臂移動距離與停留時間占比顯著增加，神經(jīng)元細(xì)胞存活數(shù)量提高，海馬神經(jīng)元細(xì)胞損傷減輕，海馬組織炎癥因子水平下降（P<0.05），海馬區(qū)CX3CL1、CX3CR1 mRNA及蛋白相對表達(dá)量升高（P<0.05）。結(jié)論 右美托咪定可改善老年大鼠肝部分切除術(shù)后POCD，其機(jī)制可能與激活CX3CL1-CX3CR1信號通路有關(guān)。

Objective To study the improvement of dexmedetomidine on postoperative cognitive dysfunction (POCD) after partial hepatectomy in aged rats by regulating the CX3CL1-CX3CR1 signaling pathway. Methods 60 aged SPF grade SD rats were randomly divided into sham operation group, positive group, model group, dexmedetomidine group, and anti-CX3CL1 + dexmedetomidine group. The rats in positive group were administrated with ibuprofen suspension 35 mg/kg by ig, 3 days before surgery, 8 h/time, for 3 consecutive days. Except for the sham operation group, rats in the other groups were underwent partial hepatectomy. Rats in the dexmedetomidine group and the anti-CX3CL1 + dexmedetomidine group were all administrated with 40 μg/kg dexmedetomidine by ip at 30 min before surgery. Rats in the sham operation group, model group and positive group were administrated with equal doses of saline by ip. After liver resection, Rats in the anti-CX3CL1 + dexmedetomidine group were stereotactically injected with 1 pmol of CX3CL1 neutralizing antibody into the lateral ventricle, and a single dose was administered. The POCD of rats were evaluated by the new forearm experiment. Nissl staining was used to observe neuronal cell damage in rat hippocampus, and the number of viable neurons were calculate. ELISA was used to detect the levels of TNF-α and IL-6 in rat hippocampus. RT-PCR and Western blotting methods were used to detect the expression of CX3CL1, CX3CR1 mRNA and protein in the hippocampus. Results Compared with the sham operation group, the proportion of new arm movement distance and residence time of rats in the model group decreased, the number of neuronal cells survived decreased, the hippocampal neuronal cells were damaged, the level of inflammatory factors in the hippocampus increased, and expression of CX3CL1 and CX3CR1 mRNA and protein in hippocampal decreased (P<0.05). After the intervention of dexmedetomidine, the proportion of new arm movement distance and residence time in POCD rats increased, the survival number of neurons was increased, the damage of hippocampal neurons was reduced, and the level of inflammatory factors was decreased (P<0.05). After dexmedetomidine intervention, the expression of CX3CL1 and CX3CR1 mRNA and protein in POCD rat hippocampus increased (P<0.05). Conclusion dexmedetomidine can improve POCD after partial hepatectomy in aged rats, and its mechanism may be related to the activation of CX3CL1-CX3CR1 signaling pathway.

R965

河南省醫(yī)學(xué)科技攻關(guān)計劃（2018020351）