目的 观察创伤应激后电针调节下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴的活性变化,并探讨下丘脑室旁核(paraventricular nucleus,PVN) FKBP5在其中的作用。方法 模拟脏器探查术建立创伤模型。60只SD雄性大鼠随机分为对照组、创伤1天组、创伤3天组、创伤7天组及电针干预组,每组12只。检测出创伤后应激高峰,给予电针作为干预,刺激双侧“三阴交”(SP-6)和“足三里”(ST-36)穴位,观察干预组与非干预组HPA轴的恢复情况。各组于相应时间点进行体温测量,免疫组化染色法检测下丘脑PVN c-fos和FOSB的表达,放射免疫分析法测定血清激素水平,Western blot检测FKBP5的表达。结果 创伤1天组与对照组相比,大鼠的体温水平明显升高[(37.90±0.21)℃ vs.(37.20±0.25)℃,P<0.05],下丘脑PVN c-fos表达(1.00±0.16 vs.2.30±0.22,P<0.01)和FOSB表达(1.00±0.08 vs.2.00±0.33,P<0.001)明显升高;与创伤1天组比较,电针干预组大鼠血清促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)(33.80±4.88 vs.28.20±3.31,P<0.05)及CORT (338.39±29.51 vs.280.85±30.39,P<0.01)、下丘脑PVN FKBP5表达(3.30±0.47 vs.2.50±0.42,P<0.05)显著下降。结论 HPA轴活性在创伤后1天达到最高,电针能下调创伤后HPA轴活性,其可能通过FKBP5发挥作用。
Objective To observe hypothalamic-pituitary-adrenal (HPA) axis activity after traumatic stress via electroacupuncture (EA) modulation,and to explore the role of FKBP5 located in hypothalamic paraventricular nucleus (PVN).Methods Sixty male rats were randomly divided into 5 groups (n=12):control,1 day after trauma,3 days after trauma,7 days after trauma and EA intervention.SP-6 and ST-36 EA were applied to the strongest stress group as the intervention in order to observe the recovery of HPA axis.Then the body temperature of each group was measured at the corresponding time points,immunohistochemical staining was used to detect the expressions of c-fos and FOSB in the hypothalamic PVN.The levels of serum hormones were measured by radioimmunoassay.Western blot was used to detect FKBP5 expression Results The body temperature of the rats in the one day trauma group was significantly higher [(37.90±0.21)℃vs. (37.20±0.25)℃,P<0.05] than that in the control group,and the expression levels of c-fos (1.00±0.16 vs.2.30±0.22,P<0.01) and FOSB (1.00±0.08 vs.2.00±0.33,P<0.001) in the hypothalamic paraventricular nucleus also increased significantly.However,compared with the strongest stress group,the serum ACTH (33.80±4.88 vs. 28.20±3.31,P<0.05) and CORT (338.39±29.51 vs. 280.85±30.39,P<0.01) of the intervention group decreased significantly.At the same time,Western blot results showed that FKBP5 (3.30±0.47 vs. 2.50±0.42,P<0.05) expression in hypothalamic PVN was also significantly reduced.Conclusions The activity of HPA axis can reach the highest level 1 day after traumatic stress,and can be significantly down-regulated by EA which may be depended on FKBP5.