大黄酚脂质体改善异氟烷致小鼠记忆功能减退的作用及对PI3K/Akt信号通路的影响
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摘要
目的:探讨大黄酚脂质体改善异氟烷致小鼠记忆功能减退的作用及对PI3K/Akt信号通路的影响。方法:昆明种小鼠80只随机分为4组:正常对照组(连续7 d腹腔注射生理盐水后吸氧2 h)、大黄酚脂质体组(连续7 d腹腔注射大黄酚脂质体10 mg·kg~(-1)后吸1. 5%异氟烷2 h)、模型组(连续7 d腹腔注射生理盐水后吸1. 5%异氟烷2 h)、大黄酚脂质体+PI3K抑制剂组(连续7 d腹腔注射大黄酚脂质体10 mg·kg~(-1)+LY294002 5 mg·kg~(-1)后吸1. 5%异氟烷2 h),麻醉结束进行Morris水迷宫试验、旷场实验和条件恐惧性实验,测定小鼠海马组织中PI3K、Akt mRNA及蛋白水平。结果:与正常对照组比较,模型组逃避潜伏期显著增加,经过原平台位置的次数、原平台象限停留的时间、运动总距离、中心区域活动时间、环境诱发僵直时间、声音诱发僵直时间、PI3K和Akt mRNA水平及蛋白水平显著降低(P <0. 05)。与模型组比较,大黄酚脂质体组和大黄酚脂质体+PI3K抑制剂组的各项指标差异均有统计学意义(P <0. 05)。大黄酚脂质体组与大黄酚脂质体+PI3K抑制剂组的各项指标差异也有统计学意义(P <0. 05)。结论:大黄酚脂质体改善异氟烷致小鼠记忆功、认知功能能减退,其机制与大黄酚脂质体活化PI3K/Akt信号通路,导致海马组织内PI3K、Akt mRNA蛋白水平升高有关。
Objective: To investigate the effect of chrysophanol liposomes on memory impairment induced by isoflurane in mice and their influence on PI3 K/Akt signaling pathway. Methods: Totally 80 Kunming mice were divided into 4 groups: the normal control group( oxygen inhalation 2 h after intraperitoneal injection of normal saline),chrysophanol liposomes group( peripheral injection of 10 mg·kg~(-1) chrysophanol liposomes for 7 d and inhalation of 1. 5% isoflurane for 2 h),the model group( peripheral injection of normal saline for 7 d and inhalation of 1. 5% isoflurane for 2 h),and chrysophanol liposomes plus PI3 K inhibitor group( peripheral injection of 10 mg·kg~(-1) chrysophanol liposome plus 5 mg·kg~(-1) LY294002 for 7 d and inhalation of 1. 5% isoflurane for 2 h). After the anesthesia,Morris water maze test,open-field experiment and conditional fear experiment were carried out. The levels of PI3 K,Akt mRNA and protein in hippocampus of mice were also determined. Results: Compared with the normal control group,in the model group,the escape latency increased significantly,and the number of times passing through the original platform,the duration of the original platform quadrant,the total distance of movement,the activity time of the central region,the time of environment-induced stiffness,the time of sound-induced stiffness,and the levels of PI3 K,Akt mRNA and protein all decreased significantly( P < 0. 05). Compared with the model group,there were significant differences in the indices of chrysophanol liposomes group and chrysophanol liposomes plus PI3 K inhibitor group( P < 0. 05). There were also significant differences in the indices between chrysophanol liposomes group and chrysophanol liposome plus PI3 K inhibitor group( P < 0. 05). Conclusion: Chrysophanol liposomes improve the memory function and cognitive function in isoflurane induced mice. The mechanism is related to the activation of PI3 K/Akt signaling pathway by chrysophanol liposomes,which leads to the increase of PI3 K and Akt mRNA levels in hippocampus.
Objective: To investigate the effect of chrysophanol liposomes on memory impairment induced by isoflurane in mice and their influence on PI3 K/Akt signaling pathway. Methods: Totally 80 Kunming mice were divided into 4 groups: the normal control group( oxygen inhalation 2 h after intraperitoneal injection of normal saline),chrysophanol liposomes group( peripheral injection of 10 mg·kg~(-1) chrysophanol liposomes for 7 d and inhalation of 1. 5% isoflurane for 2 h),the model group( peripheral injection of normal saline for 7 d and inhalation of 1. 5% isoflurane for 2 h),and chrysophanol liposomes plus PI3 K inhibitor group( peripheral injection of 10 mg·kg~(-1) chrysophanol liposome plus 5 mg·kg~(-1) LY294002 for 7 d and inhalation of 1. 5% isoflurane for 2 h). After the anesthesia,Morris water maze test,open-field experiment and conditional fear experiment were carried out. The levels of PI3 K,Akt mRNA and protein in hippocampus of mice were also determined. Results: Compared with the normal control group,in the model group,the escape latency increased significantly,and the number of times passing through the original platform,the duration of the original platform quadrant,the total distance of movement,the activity time of the central region,the time of environment-induced stiffness,the time of sound-induced stiffness,and the levels of PI3 K,Akt mRNA and protein all decreased significantly( P < 0. 05). Compared with the model group,there were significant differences in the indices of chrysophanol liposomes group and chrysophanol liposomes plus PI3 K inhibitor group( P < 0. 05). There were also significant differences in the indices between chrysophanol liposomes group and chrysophanol liposome plus PI3 K inhibitor group( P < 0. 05). Conclusion: Chrysophanol liposomes improve the memory function and cognitive function in isoflurane induced mice. The mechanism is related to the activation of PI3 K/Akt signaling pathway by chrysophanol liposomes,which leads to the increase of PI3 K and Akt mRNA levels in hippocampus.
引文
1王雅婷,仓静,方芳.影响术后认知功能障碍发生的非外科疾病因素研究进展[J].临床麻醉学杂志,2017,33(1):95-98
2张婧,陈岩,容俊芳.术后认知功能障碍影响因素的研究进展[J].中华老年多器官疾病杂志,2017,16(2):113-116
3翁嫣初,林梅,苏惠斌,等.右美托咪定对老年患者全身麻醉术后认知功能障碍及炎症反应的影响[J].国际麻醉学与复苏杂志,2017,38(2):114-117
4陈星曲,余得水,孙广运.麻醉深度对老年患者术后认知功能障碍的影响[J].四川医学,2017,38(7):844-847
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6刘展.大黄酚对地氟醚诱导老年大鼠学习认知功能损伤的影响[J].医药导报,2017,36(4):385-389
7王立华,王永利,张江伟,等.大黄酚脂质体制备方法的研究[J].中国新药杂志,2013,4(12):1452-1454
8高小芸.七氟烷与异氟烷对老年腹腔镜直肠癌切除术患者应激反应及认识功能的影响[J].医学临床研究,2018,35(6):1240-1242
9张明,荔志云,赵红斌,等.大黄酚对神经细胞缺氧损伤的保护作用[J].中华神经外科疾病研究杂志,2013,12(6):517-522
10王四海,郭桢,张秀敏,等.大黄酚对脑缺血再灌注小鼠心脏组织过氧化氢及过氧化氢酶的影响[J].河北中医,2014,24(11):54-59
11房亚兰,黄语悠,赵咏梅,等.大黄酚对局灶性脑缺血再灌注小鼠缺血半暗带区环氧化酶2和基质金属蛋白酶-表达的影响[J].首都医科大学学报,2017,38(1):47-52
12王四海,梁春利,张海红,等.大黄酚对脑缺血/再灌注小鼠脑组织NO的影响和断头抗缺氧作用[J].天津医药,2017,45(6):593-595
13李鹏,徐志鹏,米卫东.中枢炎症在术后认知功能障碍中的机制研究进展[J].北京医学,2017,39(4):386-389
14 Wang Z,Xiong L,Wang G.Insulin-like growth factor-1 protects SH-SY5Y cells againstβ-amyloid-induced apoptosis via the PI3K/AktNrf2 pathway[J].Exp Gerontol,2017,87(2):23-32
15 Gao Y,Xiao X,Zhang C,et al.Melatonin synergizes the chemotherapeutic effect of 5‐fluorouracil in colon cancer by suppressing PI3K/AKT and NF‐κB/i NOS signaling pathways[J].J Pineal Res,2017,62(2):89-91
16 Lv B,Yang X,Lv S,et al.Retraction Note to:CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERKPathways in Glioblastoma[J].Mol Neurobiol,2017,54(3):2380
17 Kim KY,Park KI,Kim SH,et al.Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/m TOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells[J].Int J Mol Sci,2017,18(5):1088-1090
18 Cao ZX,Yang YT,Yu S,et al.Pogostone Induces Autophagy and Apoptosis Involving PI3K/Akt/m TOR Axis in Human Colorectal Carcinoma HCT116 cells[J].J Ethnopharmacol,2017,202(2):20-27
19 Li X,Wu C,Chen N,et al.PI3K/Akt/m TOR signaling pathway and targeted therapy for glioblastoma[J].Oncotarget,2016,7(22):33440-33450
20 Venkatesh HS,Chaumeil MM,Ward CS,et al.Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance biomarkers of PI3K/Akt/m TOR inhibition in glioblastoma[J].NeuroOncol,2016,14(3):315-325
21 Guo R,Meng Q,Guo H,et al.TGF-β2 induces epithelial-mesenchymal transition in cultured human lens epithelial cells through activation of the PI3K/Akt/m TOR signaling pathway[J].Mol Med Rep,2016,13(2):1105-1106
22 Riquelme I,Tapia O,Leal P,et al.miR-101-2,miR-125b-2 and miR-451a act as potential tumor suppressors in gastric cancer through regulation of the PI3K/AKT/m TOR pathway[J].Cell Oncol(Dordr),2016,39(1):23-33
23 Yu Z,Zhang X,Qi L,et al.HULC long noncoding RNA silencing suppresses angiogenesis by regulating ESM-1 via the PI3K/Akt/m TOR signaling pathway in human gliomas[J].Oncotarget,2016,7(12):14429-14440
2张婧,陈岩,容俊芳.术后认知功能障碍影响因素的研究进展[J].中华老年多器官疾病杂志,2017,16(2):113-116
3翁嫣初,林梅,苏惠斌,等.右美托咪定对老年患者全身麻醉术后认知功能障碍及炎症反应的影响[J].国际麻醉学与复苏杂志,2017,38(2):114-117
4陈星曲,余得水,孙广运.麻醉深度对老年患者术后认知功能障碍的影响[J].四川医学,2017,38(7):844-847
5江波,陶利军.老年患者术后认知功能障碍相关麻醉因素研究进展[J].中华老年多器官疾病杂志,2017,16(2):157-160
6刘展.大黄酚对地氟醚诱导老年大鼠学习认知功能损伤的影响[J].医药导报,2017,36(4):385-389
7王立华,王永利,张江伟,等.大黄酚脂质体制备方法的研究[J].中国新药杂志,2013,4(12):1452-1454
8高小芸.七氟烷与异氟烷对老年腹腔镜直肠癌切除术患者应激反应及认识功能的影响[J].医学临床研究,2018,35(6):1240-1242
9张明,荔志云,赵红斌,等.大黄酚对神经细胞缺氧损伤的保护作用[J].中华神经外科疾病研究杂志,2013,12(6):517-522
10王四海,郭桢,张秀敏,等.大黄酚对脑缺血再灌注小鼠心脏组织过氧化氢及过氧化氢酶的影响[J].河北中医,2014,24(11):54-59
11房亚兰,黄语悠,赵咏梅,等.大黄酚对局灶性脑缺血再灌注小鼠缺血半暗带区环氧化酶2和基质金属蛋白酶-表达的影响[J].首都医科大学学报,2017,38(1):47-52
12王四海,梁春利,张海红,等.大黄酚对脑缺血/再灌注小鼠脑组织NO的影响和断头抗缺氧作用[J].天津医药,2017,45(6):593-595
13李鹏,徐志鹏,米卫东.中枢炎症在术后认知功能障碍中的机制研究进展[J].北京医学,2017,39(4):386-389
14 Wang Z,Xiong L,Wang G.Insulin-like growth factor-1 protects SH-SY5Y cells againstβ-amyloid-induced apoptosis via the PI3K/AktNrf2 pathway[J].Exp Gerontol,2017,87(2):23-32
15 Gao Y,Xiao X,Zhang C,et al.Melatonin synergizes the chemotherapeutic effect of 5‐fluorouracil in colon cancer by suppressing PI3K/AKT and NF‐κB/i NOS signaling pathways[J].J Pineal Res,2017,62(2):89-91
16 Lv B,Yang X,Lv S,et al.Retraction Note to:CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERKPathways in Glioblastoma[J].Mol Neurobiol,2017,54(3):2380
17 Kim KY,Park KI,Kim SH,et al.Inhibition of Autophagy Promotes Salinomycin-Induced Apoptosis via Reactive Oxygen Species-Mediated PI3K/AKT/m TOR and ERK/p38 MAPK-Dependent Signaling in Human Prostate Cancer Cells[J].Int J Mol Sci,2017,18(5):1088-1090
18 Cao ZX,Yang YT,Yu S,et al.Pogostone Induces Autophagy and Apoptosis Involving PI3K/Akt/m TOR Axis in Human Colorectal Carcinoma HCT116 cells[J].J Ethnopharmacol,2017,202(2):20-27
19 Li X,Wu C,Chen N,et al.PI3K/Akt/m TOR signaling pathway and targeted therapy for glioblastoma[J].Oncotarget,2016,7(22):33440-33450
20 Venkatesh HS,Chaumeil MM,Ward CS,et al.Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance biomarkers of PI3K/Akt/m TOR inhibition in glioblastoma[J].NeuroOncol,2016,14(3):315-325
21 Guo R,Meng Q,Guo H,et al.TGF-β2 induces epithelial-mesenchymal transition in cultured human lens epithelial cells through activation of the PI3K/Akt/m TOR signaling pathway[J].Mol Med Rep,2016,13(2):1105-1106
22 Riquelme I,Tapia O,Leal P,et al.miR-101-2,miR-125b-2 and miR-451a act as potential tumor suppressors in gastric cancer through regulation of the PI3K/AKT/m TOR pathway[J].Cell Oncol(Dordr),2016,39(1):23-33
23 Yu Z,Zhang X,Qi L,et al.HULC long noncoding RNA silencing suppresses angiogenesis by regulating ESM-1 via the PI3K/Akt/m TOR signaling pathway in human gliomas[J].Oncotarget,2016,7(12):14429-14440