摘要
目的探讨安神补脑液对抑郁症睡眠障碍大鼠下丘脑-垂体-肾上腺皮质轴的调节作用。方法选择清洁级SD雄性大鼠40只并随机分成4组:正常对照组、抑郁症睡眠障碍模型组、安神补脑液低剂量组、安神补脑液高剂量组,每组10只。分别于造模后、药物干预后7 d、14 d采用OFT法检测大鼠行为学(水平运动和垂直运动);麻醉处死大鼠取下丘脑进行称质量;采用ELISA法检测血清中促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质醇(CORT)的含量;采用免疫组化及RT-PCR法检测脑组织β-内啡肽(β-EP)和水通道蛋白4(AQP4)的表达水平。结果与正常对照组相比,模型组大鼠在造模后,体质量明显降低,但下丘脑相对质量显著升高,水平活动与垂直活动得分显著降低;血清中CRH、ACTH、CORT表达水平显著升高,脑组织β-EP和AQP4的表达水平显著降低,差异均具有统计学意义(P<0.05);与模型组相比,补脑液低剂量组大鼠体质量虽有上升,但差异无统计学意义(P>0.05),而下丘脑相对质量显著降低(P<0.05);补脑液高剂量组大鼠体质量显著升高,下丘脑相对质量显著降低(P<0.05)。安神补脑液治疗后第7天,补脑液高剂量组大鼠水平活动与垂直活动得分较模型组均显著升高(P<0.05),补脑液低剂量组大鼠水平活动与垂直活动得分较模型组虽有升高但差异无统计学意义(P>0.05);治疗14 d后,两治疗组大鼠水平活动与垂直活动与模型组比较均有明显改善(P<0.05)。两治疗组大鼠血清CRH、ACTH、CORT表达水平与模型组相比显著降低(P<0.05),而脑组织β-EP和AQP4的表达水平与模型组相比明显上升,且补脑液高剂量组β-EP和AQP4的表达水平高于补脑液低剂量组(P<0.05)。结论安神补脑液可通过调节β-EP、AQP4的表达,抑制抑郁症睡眠障碍大鼠下丘脑-垂体-肾上腺皮质轴功能亢进。
Objective To investigate the regulatory effect of Anshen Bunao Syrup on hypothalamic-pituitaryadrenal cortex axis in rats with depressive sleep disorder.Method Forty clean SD male rats were randomly divided into 4 groups:normal control group,depressive sleep disorder model group,Anshen Bunao Syrup low dose group and Anshen Bunao Syrup high dose group,with 10 rats in each group.The behavior(horizontal and vertical movements)of rats were detected by OFT after modeling,7 and 14 days after drug intervention.The rats were sacrificed under anesthesia and weighed in the hypothalamus.The contents of corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH)and cortisol(CORT)in serum were detected by ELISA.The expression levels ofβ-endorphin(β-EP)and aquaporin 4(AQP4)were detected by immunohistochemistry and RT-PCR.Result Compared with the normal control group,the weight of rats in the model group decreased significantly,but the relative weight of hypothalamus increased significantly,the scores of horizontal and vertical activities decreased significantly,while the levels of CRH,ACTH and CORT in serum increased significantly,and the expression levels ofβ-EP and AQP4 in brain tissue decreased significantly(P<0.05).Compared with the model group,the weight of rats in low dose group increased,but the difference was not statistically significant(P>0.05),while the relative weight of hypothalamus decreased significantly(P<0.05);the weight of rats in high dose group increased significantly,and the relative weight of hypothalamus decreased significantly(P<0.05).On the 7 th day after treatment,the scores of horizontal and vertical activities in the high dose group were significantly higher than those in the model group(P<0.05),while the scores of horizontal and vertical activities in the low dose group were significantly higher than those in the model group(P>0.05).After 14 days of treatment,the horizontal and vertical activities of rats in the two treatment groups were significantly improved compared with those in the model group(P<0.05).The expression levels of CRH,ACTH and CORT in the 2 treatment groups were significantly lower than those in the model group(P<0.05),while the expression levels ofβ-EP and AQP4 in brain tissue were significantly higher than those in the model group,and the expression levels ofβ-EP and AQP4 in the high dose group were higher than those in the low dose group(P<0.05).Conclusion Anshen Bunao Syrup can inhibit the hyperfunction of hypothalamus-pituitary-adrenocortical axis in depression sleep disorder rats by regulating the expression ofβ-EP and AQP4.
作者
王琦伟
许文杰
许春立
蒋瑞冲
WANG Qiwei;XU Wenjie;XU Chunli;JIANG Ruichong(Department of Neurology,The Seventh People’s Hospital of Integrated Traditional Chinese and Western Medicine Affiliated toShanghai University of Traditional Chinese Medicine,Shanghai 200137,China)
出处
《实验动物科学》
2020年第5期50-56,共7页
Laboratory Animal Science
基金
上海市卫计委课题(No.2016LQ012)。
