[1]雍 芳,狄政莉,贾晓涛,等.右美托咪定对癫痫大鼠海马神经元细胞凋亡与Toll样受体4/核因子κB信号通路的影响[J].陕西医学杂志,2023,52(2):132-135,153.[doi:DOI:10.3969/j.issn.1000-7377.2023.02.003]
　YONG Fang,DI Zhengli,JIA Xiaotao,et al.Effects of dexmedetomidine on apoptosis and TLR-4/NF-κB signaling pathway in hippocampal neurons of epileptic rats[J].,2023,52(2):132-135,153.[doi:DOI:10.3969/j.issn.1000-7377.2023.02.003]
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右美托咪定对癫痫大鼠海马神经元细胞凋亡与Toll样受体4/核因子κB信号通路的影响
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年2期
页码:
132-135,153
栏目:
基础研究
出版日期:
2023-02-05

文章信息/Info

Title:
Effects of dexmedetomidine on apoptosis and TLR-4/NF-κB signaling pathway in hippocampal neurons of epileptic rats
作者:
雍 芳; 狄政莉; 贾晓涛; 刘志勤; 顾乃兵; 郝敏锋; 燕玉娥
(西安市中心医院神经内科,陕西 西安 710004)
Author(s):
YONG Fang; DI Zhengli; JIA Xiaotao; LIU Zhiqin; GU Naibing; HAO Minfeng; YAN Yu'e
(Department of Neurology,Xi'an Central Hospital,Xi'an 710004,China)
关键词:
右美托咪定;  海马神经元;  癫痫;  细胞凋亡;  Toll样受体4;  核因子κB
Keywords:
Dexmedetomidine;  Hippocampal neurons;  Epilepsy;  Apoptosis;  Toll-like receptor 4;  Nuclear factor-κB
分类号:
R 581
DOI:
DOI:10.3969/j.issn.1000-7377.2023.02.003
文献标志码:
A
摘要:
目的:探讨右美托咪定对癫痫大鼠海马神经元细胞凋亡和Toll样受体4(TLR-4)/核因子κB(NF-κB)信号通路的影响。方法:选择45只健康SD大鼠随机分为A组、B组和C组,各15只。适应饲养1周后给予C组大鼠腹腔注射20 μg/kg右美托咪定,给予A组和B组大鼠腹腔注射等体积0.9%氯化钠溶液,均连续腹腔注射7 d。随后B组和C组采用氯化锂-匹罗卡品腹腔注射制作大鼠癫痫模型,A组大鼠不做处理。造模成功1周后进行Morris水迷宫测试。处死大鼠取脑组织,采用TUNEL技术检测海马组织神经元凋亡比例,采用酶联免疫吸附法检测海马组织中肿瘤坏死因子α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)水平,采用Western blot技术检测海马组织中NF-κB、磷酸化NF-κB(pNF-κB)、离子钙结合衔接分子1(Iba-1)、TLR-4相对表达水平。结果:C组各时间点逃避潜伏期显著长于A组,但显著短于B组(均P<0.05); C组大鼠平台穿越次数显著少于A组,多于B组(均P<0.05)。B组和C组大鼠海马组织TNF-α、IL-1β和IL-6水平均显著高于A组,C组大鼠各指标显著低于B组(均P<0.05)。C组大鼠海马神经元凋亡比例显著高于A组,但显著低于B组(均P<0.05)。C组大鼠海马组织pNF-κB、Iba-1和TLR-4蛋白相对表达水平显著高于A组,但显著低于B组(均P<0.05)。结论:右美托咪定不仅可以通过激活TLR-4/NF-κB信号通路抑制癫痫大鼠海马神经元的炎性反应,还可以通过激活TLR-4/NF-κB信号通路下调炎症因子进而抑制癫痫大鼠海马神经元细胞的凋亡,从而改善神经功能,发挥神经保护作用。
Abstract:
Objective:To investigate the effects of dexmedetomidine on apoptosis and toll-like receptor 4(TLR-4)/nuclear factor-κB(NF-κB)signaling pathway in hippocampal neurons of epileptic rats.Methods: A total of 45 healthy SD rats were randomly divided into group A,group B and group C,with 15 rats in each group.After one week of adaptation to feeding,rats in Group C were given intraperitoneal injection of 20 μg/kg dexmedetomidine,rats in group A and group B were intraperitoneally injected with the same volume of 0.9% sodium chloride solution.All rats were injected intraperitoneally for 7 days.Then group B and group C were intraperitoneally injected with lithium pilocarpine to make epilepsy model,while group A was not treated.Morris water maze test was carried out one week after successful modeling.The rats were killed to take brain tissue and detect the percentage of neuronal apoptosis in hippocampus,and the levels of TNF-α,IL-1β and IL-6 in hippocampus were detected by enzyme-linked immunosorbent assay,and the relative expression levels of NF-κB,pNF-κB,Iba-1,TLR-4 were detected by Western blot.Results:The escape latency of group C at each time point was significantly longer than that of group A,but significantly shorter than that of group B(all P<0.05).The number of platform crossing in group C was significantly less than that in group A,but more than that in group B(all P<0.05).The TNF-α,IL-1β and IL-6 levels in hippocampus of rats in group B and C were significantly higher than those in group A,and the above indexes of rats in group C were significantly lower than those in group B(all P<0.05).The percentage of apoptosis of hippocampal neurons in group C was significantly higher than that in group A,but significantly lower than that in group B(all P<0.05).The relative expression levels of pNF-κB,Iba-1 and TLR-4 proteins in hippocampus of rats in group C were significantly higher than those in group A,but significantly lower than those in group B(all P<0.05).Conclusion:Dexmedetomidine can not only inhibit the inflammatory response of hippocampal neurons in epileptic rats by activating TLR-4/NF-κB signaling pathway,but also down-regulate inflammatory factors by activating TLR-4/NF-κB signaling pathway to inhibit the apoptosis of hippocampal neurons in epileptic rats,thereby improving neurological function and providing neuroprotection.

参考文献/References:

[1] 贾东佩,李春雷.穴位埋线治疗难治性癫痫疗效及对血清GAL、PGP、MBP的影响[J].陕西中医,2019,40(4):528-530.
[2] 涂雪松.癫痫的流行病学研究[J].脑与神经疾病杂志,2017,25(8):522-528.
[3] 郑小凤.左乙拉西坦治疗癫痫发作临床疗效及对患儿认知功能的影响[J].陕西医学杂志,2020,49(10):1329-1331,1335.
[4] 郝泽林,卢晓东,王卫民,等.甘草酸对癫痫大鼠海马神经元损伤的保护作用及机制 [J].中华实验外科杂志,2019,36(2):241-245.
[5] Popp JL,Szaflarski JP,Kaur M,et al.Relationships between cognitive function,seizure control,and self-reported leisure-time exercise in epilepsy[J].Epilepsy & Behavior,2021,118(31):107900.
[6] 姚 丹,王美青,王 丹,等.保护性通气模式联合右美托咪定对老年患者全身麻醉手术期间呼吸功能、炎症应激反应的影响[J].临床和实验医学杂志,2021,20(24):2663-2667.
[7] 丁晶晶,徐金美,秦毅彬,等.右美托咪定对老年房颤非心脏手术患者心肌功能保护及脑保护的作用[J].中国老年学杂志,2021,41(8):1645-1648.
[8] 龚 拯,龙小毛,韦慧君,等.右美托咪定联合肺保护性通气策略可减轻单肺通气食管癌根治术患者的肺损伤[J].南方医科大学学报,2020,40(7):1013-1017.
[9] Zusso M,Lunardi V,Franceschini D,et al.Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-κB pathway[J].J Neuroinflammation,2019,16(1):148.
[10] 洪 震.癫痫病学研究热点[J].中华神经外科杂志,2017,50(4):245-249.
[11] 王 辛,马 茜,李丹丹,等.脑缺血大鼠脾质量指数与神经功能缺损评分及脑梗死体积的相关性[J].医学研究生学报,2015,28(9):920-924.
[12] Wu MY,Yiang GT,Liao WT,et al.Current mechanistic concepts in ischemia and reperfusion injury[J].Cell Physiol Biochem,2018,46(4):1650-1667.
[13] Franke M,Bieber M,Kraft P,et al.The NLRP3 inflammasome drives inflammation in ischemia/reperfusion injury after transient middle cerebral artery occlusion in mice[J].Brain Behav Immun,2021,92:223-233.
[14] Lu S,Chen X,Chen Q,et al.Effects of dexmedetomidine on the function of distal organs and oxidative stress after lower limb ischaemic-reperfusion in elderly patients undergoing unilateral knee arthroplasty[J].Brit J Clin Pharmacol,2021,87(11):4212-4220.
[15] 曾克非,夏婷婷.右美托咪定对绝经前期腹腔镜子宫肌瘤切除术患者麻醉诱导期镇痛及应激反应的影响[J].陕西医学杂志,2021,50(11):1433-1436.
[16] 牛廷献,罗晓红,史智勇,等.癫痫大鼠血清和脑组织IL-1β、IL-6和TNF-α水平变化[J].放射免疫学杂志,2005,18(4):256-259.
[17] Shi Y,Zhang L,Teng J,et al.HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy[J].Mol Med Rep,2018,17(4):5125-5131.
[18] Dong J,Liao Y,Wu B.TAK-242 ameliorates epileptic symptoms in mice by inhibiting the TLR4/NF-κB signaling pathway[J].Ann Transl Med,2022,10(14):795.
[19] Li X,Huang L,Liu G,et al.Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats[J].J Ethnopharmacol,2020,249:112365.
[20] Chen CH,Cheng YW,Chen YF,et al.Plasma neurofilament light chain and glial fibrillary acidic protein predict stroke in CADASIL[J].J Neuroinflammation,2020,17(1):124.

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备注/Memo

备注/Memo:
基金项目:陕西省重点研发计划项目(2022SF-418)
更新日期/Last Update: 2023-02-06