首页|异甘草素对七氟烷致老年大鼠骨折术后认知障碍的影响

异甘草素对七氟烷致老年大鼠骨折术后认知障碍的影响

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目的 观察异甘草素对七氟烷致老年大鼠骨折术后认知障碍的改善作用及对细胞外信号调节激酶 1/2(extracellular signal-regulated kinase1/2,ERK1/2)/环磷酸腺苷反应单元结合蛋白(cyclic-AMP response element binding protein,CREB)/脑源性神经营养因子(brain derived neurotrophic factor,BDNF)通路的影响。方法 将 40只骨折大鼠随机分为对照组、模型组、异甘草素组、联合组,每组10只。联合组大鼠灌胃异甘草素(15 mg·kg-1),腹腔注射PD98059(1 mg·kg-1);异甘草素组灌胃异甘草素(15 mg·kg-1),腹腔注射等量二甲基亚砜(dimethyl sulfoxide,DMSO);对照组、模型组分别灌胃、腹腔注射等量DMSO。每日1次,持续5 d。用水迷宫实验检测大鼠认知功能;检测血清炎症因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白细胞介素-1β(interleukin-1β,IL-1β);Tunel染色法观察海马神经元凋亡情况;免疫印迹法检测海马组织ERK1/2、磷酸化ERK1/2(phospho-ERK1/2,p-ERK1/2)、CREB、p-CREB、BDNF蛋白的表达。结果 与模型组[(36。26±3。95)s、(23。91±2。91)s、(5。17±0。68)次、(494。42±45。62)ng·mL-1、(600。98±60。01)ng·mL-1、(34。26%±3。96%)、(0。23±0。03)、(0。14±0。02)、(0。16±0。02)]比较,异甘草素组建模后逃避潜伏期缩短,第三象限停留时间延长,穿越原平台次数增加,血清TNF-α水平、IL-1β水平、海马神经元凋亡率降低,p-ERK1/2/ERK1/2、p-CREB/CREB 及 BDNF 蛋白表达水平升高[(14。87±1。43)s、(45。08±4。54)s、(12。31±1。77)次、(253。41±27。61)ng·mL-1、(229。04±23。55)ng·mL-1、(8。53%±1。06%)、(0。66±0。11)、(0。51±0。05)、(0。60±0。07)],P<0。05;与异甘草素组比较,联合组建模后逃避潜伏期延长,第三象限停留时间缩短,穿越原平台次数减少,血清TNF-α水平、IL-1β水平、海马神经元凋亡率升高,p-ERK1/2/ERK1/2、p-CREB/CREB及BDNF蛋白的表达水平降低[(21。06±2。72)s、(37。17±3。10)s、(7。72±0。96)次、(346。91±44。67)ng·mL-1、(391。38±34。75)ng·mL-1、(16。11%±1。84%)、(0。42±0。05)、(0。29±0。03)、(0。24±0。03)],P<0。05。结论 异甘草素可改善术后认知功能障碍、抑制炎症反应、保护海马组织神经元,激活ERK1/2/CREB/BDNF信号通路可能是其作用机制之一。
Effects of isoliquiritigenin on cognitive impairment after sevoflurane-induced fractures in aged rats
Objective To observe the improvement effect of isoliquiritigenin on sevoflurane-induced postoperative cognitive impairment in aged rats and its effect on extracellular signal-regulated kinase 1/2(ERK1/2)/cyclic adenosine monophosphate response unit binding protein(CREB)/brain-derived neurotrophic factor(BDNF)pathway.Methods Forty fractured rats were randomly divided into control group,model group,isoliquiritigenin group and combination group,10 in each group.Rats in the combination group were given isoliquiritigenin(15 mg·kg-1)by gavage,and PD98059(1 mg·kg-1)was injected intraperitoneally.The isoliquiritigenin group was given isoliquiritigenin(15 mg·kg-1)by gavage,and the same volume of dimethyl sulfoxide(DMSO)was injected intraperitoneally.The control group and the model group were given the same amount of DMSO by intragastric administration and intraperitoneal injection,respectively.Once a day,the intervention lasted for 5 days.The cognitive function of rats was detected by water maze test.The expression levels of serum inflammatory factor,such as tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)were detected.The apoptosis of hippocampal neurons was observed by Tunel staining.The expression of ERK1/2,p-ERK1/2,CREB,p-CREB and BDNF in hippocampus was detected by Western blot.Results Compared with the model group[(36.26±3.95)s,(23.91±2.91)s,(5.17±0.68)times,(494.42±45.62)ng·mL-1,(600.98±60.01)ng·mL-1,(34.26%±3.96%),(0.23±0.03),(0.14±0.02),(0.16±0.02)],the escape latency of the rats in the isoliquiritigenin group was shortened,the residence time in the third quadrant was prolonged,the number of crossing the original platform was increased,the levels of serum TNF-α,IL-1β,and the apoptosis rate of hippocampal neurons were decreased,and the p-ERK1/2/ERK1/2,p-CREB/CREB and BDNF protein were increased[(14.87±1.43)s,(45.08±4.54)s,(12.31±1.77)times,(253.41±27.61)ng·mL-1,(229.04±23.55)ng·mL-1,(8.53%±1.06%),(0.66±0.11),(0.51±0.05),(0.60±0.07)],P<0.05.Compared with the isoliquiritigenin group,the escape latency of the rats in the combined group was prolonged,the residence time in the third quadrant was shortened,the number of crossing the original platform was reduced,the levels of serum TNF-α,IL-1β,the apoptosis rate of hippocampal neurons were increased,and the p-ERK1/2/ERK1/2,p-CREB/CREB and BDNF protein were decreased[(21.06±2.72)s,(37.17±3.10)s,(7.72±0.96)times,(346.91±44.67)ng·mL-1,(391.38±34.75)ng·mL-1,(16.11%±1.84%),(0.42±0.05),(0.29±0.03),(0.24±0.03)],P<0.05.Conclusion Isoliquiritigenin can improve postoperative cognitive dysfunction,inhibit inflammatory response,and protect neurons in hippocampus,and the activation of ERK1/2/CREB/BDNF signaling pathway may be one of its mechanisms.

isoliquiritigeninsevofluranecognitive impairmentextracellular signal-regulated kinasecyclic adenosine monophosphate response unit binding proteinbrain-derived neurotrophic factor

卜亚楠、陈秋、张乐、苏孟勤

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郑州市中心医院麻醉科,郑州 450000

河南省省立医院麻醉科,郑州 450000

异甘草素 七氟烷 认知障碍 细胞外信号调节激酶 环磷酸腺苷反应单元结合蛋白 脑源性神经营养因子

河南省医学科技攻关计划项目

LHGJ20190840

2024

西北药学杂志
西安交通大学,陕西省药学会

西北药学杂志

CSTPCD
影响因子:0.912
ISSN:1004-2407
年,卷(期):2024.39(4)