河北医科大学学报 ›› 2023, Vol. 44 ›› Issue (11): 1248-1254.doi: 10.3969/j.issn.1007-3205.2023.11.002

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薰衣草精油通过抑制凋亡、上调海马BDNF/proBDNF表达改善大鼠卒中后抑郁

  

  1. 1.湖北省武汉市第三医院康复科，湖北 武汉 430061；2.湖北省武汉市第三医院麻醉科，湖北 武汉 430061

  • 出版日期:2023-11-25 发布日期:2023-12-05
  • 作者简介:程惠芳（1991-），女，湖北黄石人，湖北省武汉市第三医院初级康复治疗师，医学学士，从事肌骨康复和神经康复研究。
  • 基金资助:
    湖北省卫生健康委员会科研立项项目（WJ2019M005）

Lavender essential oil improves post-stroke depression in rats by inhibiting apoptosis and up-regulating BDNF/proBDNF expression in hippocampus

  1. 1.Department of Rehabilitation, the Third Hospital of Wuhan City, Hubei Province, Wuhan 
    430061, China； 2.Department of Anesthesiology, the Third Hospital of Wuhan City, 
    Hubei Province, Wuhan 430061, China

  • Online:2023-11-25 Published:2023-12-05

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摘要： 目的 探究薰衣草精油对脑卒中后大鼠缺血海马中脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）/前脑源性神经营养因子（pro-brain-derived neurotrophic factor，proBDNF）表达及抑郁恢复的影响。
方法 雄性SD大鼠45只随机分为对照组、模型组和干预组，每组15只。对照组在常规条件下饲养的大鼠，腹膜注射生理盐水作为对照试验；模型组，大脑中动脉闭塞/再灌注（middle cerebral artery occlusion/reperfusion，MCAO/r）模型，腹腔注射生理盐水；干预组，大鼠MCAO/r后给予薰衣草精油和运动干预。通过露天场地、强迫游泳和蔗糖偏好测试大鼠的焦虑抑郁行为。通过商业试剂盒检测大鼠氧化应激标志物水平。通过反转录聚合酶链反应（reverse transcription-polymerase chain reaction, RT-PCR）分析BDNF/proBDNF信号通路表达。通过免疫印迹发（Western blotting，WB）分析缺血海马组织中CA1区、CA3区和齿状回（dentategyrus，DG）区的BDNF/proBDNF比值。BDNF/proBDNF比值与抑郁的行为试验进行相关性分析。通过神经行为（感觉和运动）测试大鼠神经缺损。
结果 模型组大鼠静止时间长于对照组，蔗糖偏好、攀爬频率和运动距离低于对照组；干预组大鼠静止时间长于对照组，短于模型组，蔗糖偏好、攀爬频率和运动距离低于对照组，高于模型组（P＜0.05）。模型组超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽（glutathione，r-glutamyl cysteingl glycine，GSH）和抗氟离子酸性磷酸酶（fluoride resistant acid phosphatase，FRAP）水平低于对照组，丙二醛（malondialdehyde，MDA）水平高于对照组；干预组超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽（glutathione，r-glutamyl cysteingl glycine，GSH）和FRAP水平高于模型组，MDA水平低于对照组，低于模型组（P＜0.05）。模型组BDNF、神经营养素受体（neurotrophic receptor，TrkB）和微管相关蛋白（doublecortin，DCX）mRNA表达低于对照组，proBDNF和神经营养素受体P75（neurotrophic receptor P75，p75NTR） mRNA表达高于对照组；干预组BDNF、TrkB和DCX mRNA表达低于对照组，高于模型组，proBDNF和p75NTR mRNA表达高于对照组，低于模型组（P＜0.05）。模型组CA1、CA3和DG区的BDNF/proBDNF比值低于对照组;干预组CA1、CA3和DG区的BDNF/proBDNF比值高于模型组（P＜0.05）。BDNF/proBDNF比值与强迫游泳期间静止时间呈负相关（r=-0.74，P＜0.01），BDNF/proBDNF比值与蔗糖偏好呈正相关（r=0.63，P＜0.01）。模型组神经缺损评分高于对照组;干预组神经缺损评分高于对照组，低于模型组（P＜0.05）。模型组B淋巴细胞瘤-2基因相关X蛋白（Bcl-2 related X protein，Bax）/ B淋巴细胞瘤-2基因（B-cell lymphoma-2，Bcl-2）表达高于对照组，Bcl-2表达低于对照组;干预组Bax和Bax/ Bcl-2表达低于模型组，Bcl-2表达高于模型组（P＜0.05）。
结论 薰衣草精油可能通过调节BDNF和proBDNF的相对水平，改善神经功能，增强内源性抗氧化防御、抑制氧化应激途径和神经凋亡，改善PSD大鼠的抑郁样行为。


关键词: 卒中, 抑郁, 薰衣草精油

Abstract: Objective To explore the effect of lavender essential oil on the expression of brain-derived neurotrophic factor (BDNF)/pro-brain-derived neurotrophic factor (proBDNF) and the recovery of depression in the ischemic hippocampus of rats after stroke. 
Methods A total of 45 male SD rats were randomly divided into a control group, a model group, and an intervention group, with 15 rats in each group. Rats in the control group raised under conventional conditions were subjected to intraperitoneal injection of physiological saline as a control experiment. In the model group, middle cerebral artery occlusion/reperfusion (MCAO/r) model was established and rats were given intraperitoneal injection of physiological saline. In the intervention group, rats were given lavender essential oil and exercise intervention after MCAO/r. The anxiety and depression behaviors of rats were tested through outdoor venues, forced swimming, and sucrose preference. The levels of oxidative stress biomarkers in rats were detected using commercial kits, and the expression of BDNF/proBDNF signaling pathway was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The ratio of BDNF/proBDNF in CA1 region, CA3 region and dentategyrus (DG) regions of ischemic hippocampal tissue was analyzed by Western blotting (WB). The correlation analysis was performed between the BDNF/proBDNF ratio and behavioral tests for depression. Neurobehavioral (sensory and motor) testing was used to detect neural defects in rats. 
〖MM(〗〖HT6SS〗〖CM10-8〗河北医科大学学报第44卷第11期〖MM)〗
Results The stationary time of the model group was longer than that of the control group, and the sucrose preference, climbing frequency, and exercise distance were lower than those of the control group. The static time of the intervention group was longer than that of the control group and shorter than that of the model group, while the sucrose preference, climbing frequency, and exercise distance were lower than those of the control group and higher than those of the model group (P＜0.05). The levels of superoxide dismutase (SOD), glutathione，r-glutamyl cysteingl + glycine (GSH) and fluoride resistant acid phosphatase (FRAP) in the model group were lower than those in the control group, and the levels of malondialdehyde (MDA) were higher than those in the control group. The levels of SOD, GSH and FRAP in the intervention group were higher than those in the model group, while the level of MDA was lower than that in the control group and the model group (P＜0.05). The mRNA expressions of BDNF, neurotrophic receptor (TrkB) and microtubule-associated protein (DCX) in the model group were lower than those in the control group, while the mRNA expressions of proBDNF and neurotrophic receptor P75 (p75NTR) were higher than those in the control group. The mRNA expressions of BDNF, TrkB, and DCX in the intervention group were lower than those in the control group and higher than those in the model group, while the mRNA expressions of proBDNF and p75NTR were higher than those in the control group but lower than those in the model group (P＜0.05). The BDNF/proBDNF ratio in the CA1, CA3, and DG regions of the model group was lower than that of the control group, which was higher in the intervention group than in the model group (P＜0.05). The BDNF/proBDNF ratio was negatively correlated with resting time during forced swimming (r=-0.74, P＜0.01), while the BDNF/proBDNF ratio was positively correlated with sucrose preference (r=0.63, P＜0.01). The neurological deficit score in the model group was higher than that in the control group, which was higher in the intervention group than in the control group and lower than that in the model group (P＜0.05). The expression of Bcl-2 related X protein (Bax)/B-cell lymphoma-2 gene (Bcl-2) in the model group was higher than that in the control group, while the expression of Bcl-2 was lower than that in the control group. The expression of Bax and Bax/Bcl-2 in the intervention group was lower than that in the model group, while the expression of Bcl-2 was higher than that in the model group (P＜0.05). 
Conclusion Lavender essential oil may improve neurological function, enhance endogenous antioxidant defense, inhibit oxidative stress pathway and nerve apoptosis by regulating the relative level of BDNF and proBDNF, and then improve the depressive behavior of PSD rats.


Key words: stroke, depression, lavender essential oil

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