艾灸对新生小鼠脑卒中后抑郁模型色氨酸羟化酶2和单胺氧化酶A表达的影响
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摘要
目的:观察艾灸对新生小鼠脑卒中后抑郁模型中缝核色氨酸羟化酶2(TPH2)以及大脑皮质单胺氧化酶A(MAO-A)蛋白表达的影响,研究艾灸治疗新生小鼠脑卒中后抑郁的作用机制。方法:7 d新生小鼠,随机分为假手术组、脑卒中后抑郁模型组和艾灸组。采用复合刺激制备新生小鼠脑卒中后抑郁模型,即于出生后7 d给予新生小鼠脑缺血缺氧刺激,并于术后3w始给予21d慢性不可预见性温和应激。采用荧光免疫组织化学法检测小鼠中缝核TPH2蛋白表达和大脑皮质MAO-A蛋白表达。结果:脑卒中后抑郁模型组小鼠中缝核TPH2阳性细胞数[(7.43±2.44)个]低于假手术组[(29.43±9.50)个],大脑皮质MAO-A阳性细胞数[(16.57±3.21)个]高于假手术组[(2.14±0.90)个];与模型组相比,艾灸组小鼠中缝核TPH2阳性细胞数[(23.29±8.71)个]增多,大脑皮质MAO-A阳性细胞数[(7.43±3.26)个]减少。结论:艾灸改善新生小鼠脑卒中后抑郁的效果,可能与其提高中缝核TPH2表达、降低大脑皮质MAO-A表达有关。
Objective:The effects of moxibustion on the expressions of typtophan hydroxylase-2(TPH2) in median raphe nuclei and monoamine oxidase A(MAO-A) in the cortex were investigated in order to explore the mechanism of its antidepressant effect in post-stroke depression mice.Methods:Post-stroke depression model was induced by hypoxia and ischemia at 7 d postnatal in combination with chronic unexpected mild stress(CUMS) for 21 days since 3 weeks after surgery.Immunofluorescent staining was employed to detect the expression of TPH2 and MAO-A.Results:TPH2-positive cells(7.43±2.44)in median raphe nuclei decreased in model group compared to those in sham group(29.43±9.50),and MAO-A-positive cells(16.57±3.21)in cerebral cortex increased in model group compared to those in sham group(2.14±0.90),while TPH2-positive cells(23.29±8.71)in median raphe nuclei increased and MAO-A-positive cells(7.43±3.26)in cerebral cortex decreased in moxibustion-treated group compared to those in model group.Conclusion:Moxibustion improved the symptoms of post-stroke depression,which might be through regulating the expressions of TPH2 and MAO-A.
Objective:The effects of moxibustion on the expressions of typtophan hydroxylase-2(TPH2) in median raphe nuclei and monoamine oxidase A(MAO-A) in the cortex were investigated in order to explore the mechanism of its antidepressant effect in post-stroke depression mice.Methods:Post-stroke depression model was induced by hypoxia and ischemia at 7 d postnatal in combination with chronic unexpected mild stress(CUMS) for 21 days since 3 weeks after surgery.Immunofluorescent staining was employed to detect the expression of TPH2 and MAO-A.Results:TPH2-positive cells(7.43±2.44)in median raphe nuclei decreased in model group compared to those in sham group(29.43±9.50),and MAO-A-positive cells(16.57±3.21)in cerebral cortex increased in model group compared to those in sham group(2.14±0.90),while TPH2-positive cells(23.29±8.71)in median raphe nuclei increased and MAO-A-positive cells(7.43±3.26)in cerebral cortex decreased in moxibustion-treated group compared to those in model group.Conclusion:Moxibustion improved the symptoms of post-stroke depression,which might be through regulating the expressions of TPH2 and MAO-A.
引文
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[3] 骆彤,汪武生.艾灸治疗中风后抑郁症的临床研究[J].中国中医药现代远程教育,2011,9(8):140-141.
[4] 肖爱娇,欧阳昕,陈明人.艾灸对新生小鼠脑卒中后抑郁模型体质量和行为学的影响[J].江西中医药大学学报,2018,30(1):74-77.
[5] Walther DJ,Peter JU,Bashammakh S,et al.Synthesis of serotonin by a second tryptophan hydroxylase isoform[J].Science,2003,299(5603):76.
[6] Xiao AJ,Chen W,Xu B,et al.Marine Compound Xyloketal B Reduces Neonatal Hypoxic-Ischemic Brain Injury[J].Marine Drugs,2015,13(1):29-47.
[7] Xu B,Xiao AJ,Chen W,et al.Neuroprotective Effects of PSD-95 Inhibitor in Neonatal Hypoxic-Ischemic Brain Injury[J].Molecular Neurobiology,2016,53(9):5962-5970.
[8] 肖爱娇,康明非,汪建民,等.新生小鼠缺氧缺血性脑病脑组织caspase-3表达的变化[J].天津医药,2015,43(10):1116-1118.
[9] Willner P,Towell A,Sampson D,et al.Reduction of sucrose preference by chronic unpredictable mild stress,and its restoration by a tricyclic antidepressant[J].Psychopharmacology (Berl),1987,93(3):358-364.
[10] 李忠仁.实验针灸学[M].北京:中国中医药出版社,2003:327-329.
[11] 刘福友,杨石,陈卫垠,等.脑卒中后抑郁大鼠模型的建立[J].中国临床康复,2006,10(42):91-94.
[12] 洪华,黄如训,王庭槐,等.脑卒中后抑郁大鼠模型的建立[J].中国临床康复,2002,6(9):1266-1267.
[13] 倪贵华,邵蓓,范虹.卒中后抑郁实验动物模型的研究[J].温州医学院学报,2006,36(6):524-526.
[14] 唐启盛,裴清华,侯秀娟,等.脑卒中后抑郁状态动物模型的建立[J].北京中医药大学学报,2004,27(3):33-36.
[15] 肖爱娇,康明非,陈日新,等.热敏灸对抑郁症模型大鼠行为学的影响[J].江西中医学院学报,2011,23(4):24-28.
[16] 肖爱娇,邹宏昌.艾灸对抑郁症模型大鼠色氨酸羟化酶2基因表达与单胺氧化酶活性的影响[J].中华行为医学科学与脑科学杂志,2012,21(2):126-128.
[17] 肖爱娇,韩志芬,黄景斌,等.抑郁症大鼠海马5-羟色胺含量及中缝核色氨酸羟化酶-2表达变化的研究[J].中华精神科杂志,2008,41(3):180-183.
[18] Shishkina GT,Kalinina TS,Dygalo NN.Up-regulation of tryptophan hydroxylase-2 mRNA in the rat brain by chronic fluoxetine treatment correlates with its antidepressant effect[J].Neuroscience,2007,150(2):404-412.
[19] Kim SW,Park SY,Hwang O.Up-Regulation of Tryptophan Hydroxylase Expression and Serotonin Synthesis by Sertraline[J].Mol Pharmacol,2002,61 (4):778-785.