目的 探讨异氟醚吸入麻醉调控星形胶质细胞活化对围术期小鼠神经认知功能的影响。方法 C57BL/6小鼠80只随机分为对照组、2%异氟醚组、手术组、2%异氟醚+手术组,每组20只。Morris水迷宫实验评估小鼠术后1、3、7 d认知功能,测定海马组织炎性反应及凋亡相关因子水平,免疫荧光染色观察星形胶质细胞活化情况,TUNEL法检测细胞凋亡。结果 术后1、3、7 d,与2%异氟醚组和手术组比较,2%异氟醚+手术组小鼠逃避潜伏期[(77.36±13.48)s vs.(66.71±4.54)s、(64.47±4.43)s]、[(51.63±8.43)s vs.(46.37±5.69)s、(45.72±5.71)s]、[(30.85±4.56)s vs.(21.13±3.24)s、(22.36±3.18)s]显著延长,目标象限停留时间[(13.16±4.25)s vs.(35.36±4.48)s、(36.14±4.42)s]、[(19.48±6.37)s vs.(37.64±6.33)s、(37.15±6.28)s]、[(23.69±5.54)s vs.(39.15±6.34)s、(38.63±5.43)s]显著缩短,海马组织肿瘤坏死因子-α、白细胞介素-6和半胱氨酸天冬氨酸蛋白酶-3表达水平显著升高,海马组织胶质纤维酸性蛋白阳性细胞数[(11.97±1.35)vs.(14.15±1.48)、(15.67±1.51)]、[(34.74±1.52)vs.(31.92±1.44)、(31.96±1.52)]、[(35.69±1.48)vs.(32.14±1.51)、(31.96±1.52)]显著增加,海马神经元细胞凋亡率[(56.71±1.87)% vs.(48.63±1.45)%、(48.34±1.69)%]、[(59.64±1.57)% vs.(49.63±1.51)%、(49.45±1.58)%]、[(63.49±2.62)% vs.(50.68±2.45)%、(50.38±2.44)%]显著增高(P<0.05)。结论 异氟醚吸入麻醉可引起围术期小鼠认知功能下降,其机制可能与促进海马星形胶质细胞活化、诱导神经元凋亡、加重神经炎性反应水平有关。
Abstract
Objective To investigate the effect of isoflurane inhalation anesthesia on perioperative neurocognitive function of mice and the mechanism. Methods C57BL/6 mice were randomly divided into the control group, 2% isoflurane group, surgery group and 2% isoflurane + surgery group, with 20 mice in each. Morris water maze test was used to evaluate the cognitive function of mice one, three and seven days after surgery. The levels of inflammation and apoptosis related factors in the hippocampus were measured. The activation of astrocytes was observed with immunofluorescence staining while apoptosis was detected by TUNEL. Results Compared with the 2% isoflurane group and surgery group, the escape latency [(77.36±13.48)s vs. (66.71±4.54)s, (64.47±4.43)s],[(51.63±8.43)s vs. (46.37±5.69)s, (45.72±5.71)s],[(30.85±4.56)s vs. (21.13±3.24)s, (22.36±3.18)s] of the 2% isoflurane + surgery group was significantly increased one, three and seven days after operation, while the time spent in the target quadrant[(13.16±4.25)s vs. (35.36±4.48)s, (36.14±4.42)s],[(19.48±6.37)s vs. (37.64±6.33)s, (37.15±6.28)s], [(23.69±5.54)s vs. (39.15±6.34)s, (38.63±5.43)s] was significantly shortened. The expression of TNF-α in the hippocampus was significantly decreased, while the expressions of IL-6 and caspase-3 were significantly increased. The number of GFAP positive cells [(11.97±1.35) vs. (14.15±1.48), (15.67±1.51)], [(34.74±1.52) vs. (31.92±1.44), (31.96±1.52)],[(35.69±1.48) vs. (32.14±1.51), (31.96±1.52)] and the apoptosis rate of hippocampal neurons [(56.71±1.87)% vs. (48.63±1.45)%, (48.34±1.69)%],[(59.64±1.57)% vs. (49.63±1.51)%, (49.45±1.58)%],[(63.49±2.62)% vs. (50.68±2.45)%, (50.38±2.44)%] were significantly increased (P<0.05). Conclusions Isoflurane inhalation anesthesia can cause the decline of cognitive function in perioperative mice, and the mechanism may be related to promoting the activation of hippocampal astrocytes, inducing neuronal apoptosis and aggravating the level of neuroinflammation.
关键词
异氟醚 /
吸入麻醉 /
围术期神经认知紊乱 /
神经认知功能 /
星形胶质细胞
Key words
isoflurane /
inhalation anesthesia /
perioperative neurocognitive disorder /
neurocognitive function /
astrocytes
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] GiordanoG,Pugliese F,Bilotta F.Perioperative neurocognitive disorder: comment[J]. Anesthesiology, 2020,133(1): 243-244.
[2] 汪 懿,怀 昌,金孝岠,等.右美托咪定对全身麻醉下行非心脏手术老年患者术后早期认知功能影响的Meta分析[J].临床麻醉学杂志, 2017,33(1):45-51.
[3] Wang D S, Terrando N, Orser B A. Targeting microglia to mitigate perioperative neurocognitive disorders[J]. Br J Anaesth, 2020, 125(3): 229-232.
[4] Antila H, Ryazantseva M, Popova D, et al. Isoflurane produces antidepressant effects and induces TrkB signaling in rodents[J].Sci Rep, 2017,7(1):7811-7811.
[5] 刘鹏飞, 胡艳婷, 李天佐,等. 阿托伐他汀预处理对异氟醚麻醉小鼠认知功能的影响[J]. 中华麻醉学杂志, 2017, 37(9):1082-1086.
[6] Liddelow S A, Guttenplan K A, Clarke L E, et al. Neurotoxic reactive astrocytes are induced by activated microglia[J].Nature, 2017,541(7638):481-487.
[7] 刘佩蓉,张 瑜,刘春亮,等.电针对肝叶切除术后大鼠认知功能及海马胶质细胞的影响[J].上海针灸杂志,2020,39(2):226-231.
[8] 周加慧,于 洋,毕燕琳,等. 海马miRNA-320在小鼠围术期神经认知障碍中的作用[J]. 中华麻醉学杂志, 2020, 40(9): 1075-1078.
[9] Wang X, Chen L, Xu Y, et al. Gastrodin alleviates perioperative neurocognitive dysfunction of aged mice by suppressing neuroinflammation[J]. Eur J Pharmacol, 2020, 892(44):173734.
[10] Pradoldej S, Norris C M. Ca2+, Astrocyte activation and calcineurin/NFAT signaling in age-related neurodegenerative diseases[J].Front Aging Neurosci, 2018, 10(4):199.
[11] Awal M R, Wirak G S, Gabel C V, et al. Collapse of global neuronal states in caenorhabditis elegans under isoflurane anesthesia[J]. Anesthesiology,2020,133(1):133-144.
[12] 冯海妹,韦雪梅.异氟醚对老龄大鼠认知功能障碍、GSK-3β及炎性因子的影响[J].标记免疫分析与临床,2019,26(4):170-173,179.
[13] Miao H, Dong Y, Zhang Y, et al. Anesthetic isoflurane or desflurane plus surgery differently affects cognitive function in Alzheimer’s disease transgenic mice[J].Mol Neurobiol, 2017, 55(7): 5623-5638.
[14] 马 斌, 迟 良, 胡胜超,等. 异氟醚对幼年小鼠神经认知功能损伤的研究[J].中国兽医杂志,2019, 55(7): 88-90,94.
[15] 秦 起,李 芮,曾庆繁.白藜芦醇对老年大鼠术后认知功能的影响[J].贵阳医学院学报,2019, 44(4): 427-430,452
[16] 贾 强.全麻复合硬膜外麻醉对胃癌根治术患者应激及炎性反应的影响[J].中国实用医药,2019,14(23):20-22.
[17] 马 競,王菲菲,彭 勉.帕瑞昔布对肝部分切除术老年大鼠海马炎症反应的影响[J].临床麻醉学杂志,2017,33(3):286-289.
[18] Miles B, Vikram P, Nathaniel G, et al. The effect of propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels: results from a randomized trial[J].Front Immunol, 2017,8(4):1528.
[19] 杨尚泽,李 瑾,朱晓秋,等.利多卡因减轻异氟醚对Fischer344老年大鼠海马神经元线粒体的损伤[J].中华实验外科杂志,2017,34(1):72-74.
[20] 郭 莹,潘 波,黄绍强.瑞芬太尼改善异氟醚致新生大鼠神经毒性的机制[J].复旦学报(医学版), 2019,46(1): 8-13.
基金
安徽省重点研究与开发项目(201904a07020108)
PDF(1940 KB)
