目的: 评价不同剂量舒芬太尼对围术期认知功能紊乱老年大鼠术后认知受损的影响。方法: 60只18～22月龄老年大鼠,采用随机数字表法分成6组:对照组、围术期神经认知紊乱(PND)模型组(脾切除)、舒芬太尼A组(脾切除+舒芬太尼1 μg·kg-1)、舒芬太尼B组(脾切除+舒芬太尼2 μg·kg-1)、舒芬太尼C组(脾切除+舒芬太尼4 μg·kg-1),舒芬太尼D组(脾切除+舒芬太尼8 μg·kg-1),每组10只。通过脾切除手术构建SD雄性老年大鼠PND模型。首先利用Morris水迷宫进行连续5 d的空间获得性实验后,于第6天对除了对照组以外的其它各组老年大鼠进行模型构建和(或)术前腹腔注射舒芬太尼干预。所有老年大鼠均于术后的第1、3和7天再对老年大鼠进行空间记忆测试。结果: 空间获得性实验会使老年大鼠对于平台位置的记忆随着时间的延长而逐渐加深(P＜0.05),大鼠对平台位置获得了有效的记忆,且各组之间没有差异。参考记忆测试结果表明对照组与其它各组术后的空间记忆能力的差异有统计学意义(P＜0.05);模型组与舒芬太尼B组、舒芬太尼C组、舒芬太尼D组术后的空间记忆能力的差异有统计学意义(P＜0.05);舒芬太尼C组与除了对照组之外其它各组的空间记忆能力的差异有统计学意义(P＜0.05)。结论: 不同剂量舒芬太尼对老年大鼠术后空间记忆的影响不同,腹腔注射4 μg·kg-1舒芬太尼可以明显改善脾切除PND模型大鼠空间记忆能力,改善术后认知功能。
Objective: To evaluate the effects of different doses of sufentanil on postoperative cognitive impairment in aged rats with perioperative cognitive dysfunction. Methods: Sixty aged (18-22 months) rats were randomly divided into 6 groups using a random number table method: control group, PND model group (splenectomy), sufentanil group A (splenectomy+sufentanil 1 μg·kg-1), sufentanil group B (splenectomy+sufentanil 2 μg·kg-1), sufentanil group C (splenectomy+sufentanil 4 μg·kg-1), sufentanil group D (splenectomy+sufentanil 8 μg·kg-1), with 10 rats in each group. First, the Morris water maze was used to conduct space acquisition experiments for 5 consecutive days of all the groups. On the 6th day, model construction and/or preoperative sufentanil intraperitoneal intervention were performed on all the other groups of aged rats except for the control group. All aged rats were tested for spatial memory on the 1, 3 and 7 days after surgery. Results: Space-acquired experiments made the memory of platform position in aged rats gradually deepen with time (P＜0.05), and rats gained effective memory of platform position, there was no difference between the groups. The reference memory test results showed that the difference in spatial memory between the control group and each of the other groups was statistically significant (P＜0.05). There was significant difference in spatial memory ability between the model group and the sufentanil B group, the sufentanil C group and the sufentanil D group (P＜0.05). In addition to the control group, the spatial memory ability of the sufentanil C group was significantly different from that of the other groups (P＜0.05). Conclusion: Different doses of sufentanil have different effects on postoperative spatial memory in elderly rats, while intraperitoneal injection of 4 μg·kg-1 sufentanil can significantly improve the spatial memory ability and postoperative cognitive function of splenectomy PND model rats.
[1] Steinmetz J, Christensen KB, Lund T, et al. Long-term consequences of postoperative cognitive dysfunction[J]. Anesthesiology, 2009,110(3):548-555.
[2] Khachaturian AS, Hayden KM, Devlin JW, et al. International drive to illuminate delirium: A developing public health blueprint for action[J]. Alzheimers Dement, 2020,16(5):711-725.
[3] Sanders RD, Maze M. Neuroinflammation and postoperative cognitive dysfunction: Can anaesthesia be therapeutic[J]. Eur J Anaesthesiol, 2010,27(1):3-5.
[4] Olotu C. Postoperative neurocognitive disorders[J]. Curr Opin Anaesthesiol, 2020,33(1):101-108.
[5] Subramaniyan S, Terrando N. Neuroinflammation and perioperative neurocognitive disorders[J]. Anesth Analg, 2019,128(4):781-788.
[6] Chen XH, Gao F, Lin CC, et al. mTOR-mediated autophagy in the hippocampus is involved in perioperative neurocognitive disorders in diabetic rats[J]. CNS Neurosci Ther, 2022,28(4):540-553.
[7] Zhao WX, Xu ZP, Cao JB, et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice[J]. J Neuroinflammation, 2019,16(1):230.
[8] Li SY, Xia LX, Zhao YL, et al. Minocycline mitigates isoflurane-induced cognitive impairment in aged rats[J]. Brain Res, 2013,1496:84-93.
[9] Qian XL, Zhang W, Liu MZ, et al. Dexmedetomidine improves early postoperative cognitive dysfunction in aged mice[J]. Eur J Pharmacol, 2015,746:206-212.
[10] Lian YH, Fang J, Zhou HD, et al. Sufentanil preconditioning protects against hepatic ischemia-reperfusion injury by suppressing inflammation[J]. Med Sci Monit, 2019,25:2265-2273.
[11] 王戡,潘芳,冯艺,等. 氟比洛芬酯复合舒芬太尼术后镇痛效果及抗炎作用的研究[J]. 临床麻醉学杂志,2011,27(10):941-943.
[12] 柳培雨,田毅,李海,等. 两种浓度七氟烷联合舒芬太尼后处理对创伤性失血性休克炎性反应的影响[J]. 武警医学,2014,25(2):123-126.
[13] 马锐,路志红,熊利泽,等. 舒芬太尼预先给药对大鼠急性局灶性脑缺血-再灌注损伤的保护作用[J]. 临床麻醉学杂志,2009,25(11):978-979.
[14] 周有东,马金阳,黄松,等. 舒芬太尼对大鼠蛛网膜下腔出血后脑损伤的保护作用[J]. 中国临床神经外科杂志,2021,26(7):531-536.
[15] 余裕钦,胡年春,段吉安,等. 舒芬太尼预处理对脊髓损伤模型小鼠的神经保护[J]. 中国组织工程研究,2016,20(40):5966-5972.
[16] 赵智茹,李荣. 舒芬太尼预处理对老年患者联合麻醉下行髋关节手术术后认知功能的影响[J]. 包头医学院学报,2018,34(9):37-39.
[17] 王健,李荣. 舒芬太尼对老年糖尿病患者下肢骨关节置换术后认知功能的影响[J]. 系统医学,2019,4(15):43-46.
[18] Huang CX, Ng OT, Ho YS, et al. Effect of continuous propofol infusion in rat on tau phosphorylation with or without temperature control[J]. J Alzheimers Dis, 2016,51(1):213-226.
[19] Goveia CS, Miranda DB, Oliveira LVB, et al. Dexmedetomidine reduces postoperative cognitive and behavioral dysfunction in adults submitted to general anesthesia for non-cardiac surgery: meta-analysis of randomized clinical trials[J]. Braz J Anesthesiol, 2021,71(4):413-420.
[20] Cao YY, Li ZQ, Ma LJ, et al. Isoflurane-induced postoperative cognitive dysfunction is mediated by hypoxia-inducible factor-1α-dependent neuroinflammation in aged rats[J]. Mol Med Rep, 2018,17(6):7730-7736.
[21] 彭勉,鲁胜强,王焱林,等. 腹腔手术对老龄大鼠认知功能的影响[J]. 武汉大学学报(医学版),2010,31(6):735-738.
[22] 毕立伟,张析哲,孙义,等. 舒芬太尼的药理作用和临床应用进展[J]. 实用医技杂志,2015,22(1):48-50.
[23] 黄继汉,黄晓晖,陈志扬,等. 药理试验中动物间和动物与人体间的等效剂量换算[J]. 中国临床药理学与治疗学,2004,9(9):1069-1072.
[24] 程岑,顾尔伟,鲁显福,等. 舒芬太尼后处理对大鼠局灶性脑缺血再灌注损伤的保护作用[J]. 安徽医科大学学报,2014,49(7):883-886.
[25] 强子耘. 舒芬太尼预处理对大鼠脊髓缺血再灌注损伤中运动功能及 MPO、IL-6、IL-15的影响[D].沈阳:中国医科大学,2019.
[26] 强子耘,陈凤收,贾慧,等. 舒芬太尼预处理对大鼠脊髓缺血再灌注损伤中炎性因子 MPO,IL-6,IL-15 的影响[J].现代生物医学进展,2019,19(16):3013-3017.
