目的 观察右美托咪定通过调节CX3CL1-CX3CR1信号通路对老年大鼠肝部分切除术术后认知功能障碍（POCD）的改善作用。方法 60只SPF级老年SD大鼠随机分为假手术组、模型组、阳性对照组、右美托咪定组和CX3CL1抗体+右美托咪定组。阳性对照组大鼠于术前3 d给予布洛芬混悬液35 mg/kg，ig给药，8 h/次，连续3 d；除假手术组外，各组大鼠均实施肝部分切除术，右美托咪定组和CX3CL1抗体+右美托咪定组术前30 min均以40 μg/kg右美托咪定ip给药，假手术组、模型组及阳性对照组予以ip等剂量生理盐水。肝脏切除后，CX3CL1抗体+右美托咪定组侧脑室立体定位注射CX3CL1中和抗体1 pmol，单次给药。新异臂探索实验评价各组大鼠认知功能；Nissl染色观察各组大鼠海马组织神经元细胞损伤；ELISA法检测各组大鼠海马组织肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）水平；qRT-PCR及Western blotting检测海马区CX3CL1、CX3CR1 mRNA及蛋白的表达。结果 与假手术组比较，模型组大鼠新异臂移动距离与停留时间占比下降，神经元细胞存活数量减少，海马神经元细胞损伤，海马组织炎症因子水平升高，海马区CX3CL1、CX3CR1 mRNA及蛋白相对表达量降低（P<0.05），经右美托咪定干预后POCD大鼠新异臂移动距离与停留时间占比显著增加，神经元细胞存活数量提高，海马神经元细胞损伤减轻，海马组织炎症因子水平下降（P<0.05），海马区CX3CL1、CX3CR1 mRNA及蛋白相对表达量升高（P<0.05）。结论 右美托咪定可改善老年大鼠肝部分切除术后POCD，其机制可能与激活CX3CL1-CX3CR1信号通路有关。

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

河南省医学科技攻关计划（2018020351）