摘要
目的:观察腹部推拿对慢性应激所致慢性疲劳综合征(CFS)模型大鼠海马-下丘脑-垂体-肾上腺(海马-HPA)轴的影响,探讨其对海马神经的重塑作用机制。方法:选取成年健康Wistar雌性大鼠60只,分为正常组、模型组和实验组,每组20只,模型组和实验组大鼠采用复合应激方法复制CFS模型,实验组大鼠模型制作成功后进行腹部推拿干预,正常组大鼠不予以任何处理。采用行为学效应指标验证模型,电镜观察大鼠海马神经元超微形态表现,免疫组织化学法检测大鼠海马组织中FK506结合蛋白(FKBPs)、糖皮质激素受体(GR)和N-甲基-D-天冬氨酸受体(NMDAR)阳性表达率,酶联免疫吸附测定法(ELISA)检测大鼠血清中促肾上腺皮质激素(ACTH)、皮质醇(CORT)、促肾上腺皮质激素释放激素(CRH)和糖皮质激素(GC)水平。结果:大鼠行为学效应指标检测,与正常组比较,模型组和干预前实验组大鼠悬挂不动时间明显延长(P<0.05),力竭游泳时间明显缩短(P<0.05),水平运动速度明显降低(P<0.05);与模型组比较,干预后实验组大鼠悬挂不动时间明显缩短(P<0.05),力竭游泳时间明显延长(P<0.05),水平运动速度明显增加(P<0.05)。电镜下观察,与正常组比较,模型组大鼠海马神经元胞体缩小,部分神经元胞膜内陷,有凋亡小体形成;与模型组比较,实验组大鼠海马神经元病变明显减轻。与正常组比较,模型组大鼠海马组织中FKBPs、GR和NMDAR阳性表达率明显降低(P<0.05);与模型组比较,实验组大鼠海马组织中FKBPs、GR和NMDAR阳性表达率明显升高(P<0.05)。与正常组比较,模型组大鼠血清中ACTH、CORT、CRH和GC水平明显升高(P<0.05);与模型组比较,实验组大鼠血清中ACTH、CORT、CRH和GC水平明显降低(P<0.05)。结论:腹部推拿疗法可以促进慢性应激反应所致的损伤性海马神经重塑,降低ACTH、CORT和CRH激素水平,通过FKBPs-GR-NMDAR通路维持海马-HPA轴负反馈平衡。
Objective:To observe the effect of abdominal manipulation on the remodeling of hippocampal neurons in the model rats with chronic stress-induced chronic fatigue syndrome(CFS),and to analyze the mechanism of negative feedback regulation of hippocampus-hypothalamic-pituitary-adrenal axis(hippocampus-HPA axis).Methods:A total of 60 healthy adult female Wistar rats were selected and divided into normal group,model group and experimental group,there were 20 rats in each group.The rats in model group and experimental group were used to establish the CFS models by multiple stress,and abdominal manipulation intervention was performed in experiment group after model establishment,while the rats in normal group received no treatment.The behavior effect indicators were used to verify the models;the urtramicromorphology of hippocampal neurons of the rats was observed by electron microscope.The positive expression rates of FK506 binding protein(FKBPs),glucocorticoid receptor(GR)and N-methyl-D-aspartate receptor(NMDAR)were detected by immunohistochemical method,and the serum levels of adrenocorticotropic hormone(ACTH),cortisol(CORT),corticotropin releasing hormone(CRH)and glucocorticoid(GC)of the rats were detected by ELISA method.Results:The behavior effect indicator examination results showed the time for immobility of the rats in model group and experiment group before abdominal manipulation was longer than that in normal group(P<0.05),and the time for exhaustive swimming and the speeds of horizontal movement of the mice in model group and experiment group were lower than those in normal group(P<0.05);compared with model group,the time for immobility of the rats in experiment group was significantly shortened(P<0.05),the exhaustive swimming time was significantly prolonged(P<0.05),and the horizontal movement speed was significantly increased(P<0.05).Compared wtih normal group,shrinkage of hippocampal neurons,some invaginated neurons and apoptotic bodies were observed in model group under electron microscope;compared with model group,the hippocampal neurons in experiment group were significantly alleviated.Compared with normal group,the positive expression rates of FKBPs,GR and NMDAR in the hippocampus tissue of the rats in model group and experiment group were significantly decreased(P<0.05);compared with model group,the positive expression rates of FKBPs,GR and NMDAR in the hippocampus tissue of the rats in experiment group were significantly increased(P<0.05).Compared with normal group,the serum levels of ACTH,CORT,CRH and GC of the rats in model group were significantly increased(P<0.05);compared with model group,the serum levels of ACTH,CORT,CRH and GC of the rats in experiment group were significantly decreased(P<0.05).Conclusion:Abdominal manipulation can promote the remodeling of damaged hippocampal neurons caused by stress response,reduce the levels of ACTH,CORT and CRH,and maintain the negative feedback balance of hippocampus-HPA axis through regulating FKBPs-GR-NMDAR pathway.
作者
潘明柱
李建
荣兵
贾峻
李华南
PAN Mingzhu;LI Jian;RONG Bing;JIA Jun;LI Huanan(Department of Tuina,First Affiliated Hospital,Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China)
出处
《吉林大学学报(医学版)》
CAS
CSCD
北大核心
2021年第4期842-848,共7页
Journal of Jilin University:Medicine Edition
基金
国家自然科学基金项目(81873393)。