电针对慢性应激抑郁模型大鼠糖皮质激素及其受体基因表达的影响

Effect of Electroacupuncture of "Baihui"(GV 20)-"Yintang" (EX-HN 3) on the Expression of Glucocorticoid and Glucocorticoid Receptor mRNA of the Chronic Stress Model Rats

目的:观察电针对慢性应激模型大鼠糖皮质激素及其受体的影响,进而探讨电针抗抑郁的作用机制。方法:SD大鼠随机分为空白组、模型组、百优解组、束缚组、电针组、糖皮质激素拮抗剂组、电针加糖皮质激素拮抗剂组,每组10只。采用慢性应激结合孤养21d造模。选取"百会"透"印堂"穴电针治疗慢性应激模型大鼠,用糖皮质激素受体拮抗剂RU486阻断下丘脑-垂体-肾上腺(HPA)轴的负反馈通路。放射免疫法检测肾上腺皮质酮含量,实时荧光定量逆转录-聚合酶链式反应法检测海马、下丘脑、垂体糖皮质激素受体(GR)mRNA的表达。结果:与空白组比较,束缚组大鼠肾上腺皮质酮的分泌明显增多(P<0.05),而电针组与束缚组比较皮质酮的过度分泌明显降低(P<0.05)。束缚组大鼠GRmRNA在海马、下丘脑及垂体的表达显著下降(P<0.05),电针组与束缚组比较海马、下丘脑、垂体GR的生成增多(P<0.05)。以上两指标,模型组和糖皮质激素拮抗剂组的变化与束缚组一致;与模型组比较,百优解组仅可明显升高海马GRmRNA的表达(P<0.05);与糖皮质激素拮抗剂组比较,电针加糖皮质激素拮抗剂组可降低肾上腺皮质酮的含量(P<0.05),升高海马GRmRNA的表达(P<0.05),但其降低肾上腺皮质酮含量和升高下丘脑、垂体GRmRNA表达的作用均不及电针组(P<0.05)。结论:电针对糖皮质激素的过度分泌有直接的调控作用,并可通过增强GRmRNA的表达,改善HPA轴负反馈中枢的功能障碍。当HPA轴负反馈通路被阻断后,电针的作用减弱。

Objective To observe the effect of electroacupuncture （EA） on the expression of glucocorticoid （GC） mRNA and GC in the hippocampus,hypothalamus and pituitary in depression rats so as to study its mechanism underlying EA-resisting depression. Methods Seventy SD rats were randomized into normal control,modeI,Fluoxetine （Flu） ,constraint-stress,EA,RU 486 （an antagonist of GC） and EA＋ RU 486 groups （n = 10/group）. Chronic depression model was established by lonely raising and chronic unpredictable mild stress for 21 days. EA （2 Hz,0.6 mA） was applied to ＂Baihui＂ （GV 20） and ＂Yintang＂ （EX-HN 3） for 20 min, once daily for 21 days. Subcutaneous injection of RU 486 （20 mg/kg） was given to the rats from the 14th day on and continuously for 7 days in order to block the negative feedback reflex of hypothalamus-pituitary-adrenal （HPA） axis. Cortisol （CORT） content of the adrenal gland tissue was detected by radioimmunassay. The expression of GO receptor （GR）mRNA in the hippocam- pus, hypothalamus and pituitary tissues was determined by real-time quantitative reverse transcription-polymerase chain reaction （RT-PCR）. Results Compared with the normal control group,adrenal CORT content of model group was increased significantly （P〈0.05） ,and in comparison with model group, adrenal CORT level of EA group decreased evidently （P〈0.05）. Comparison between the RU 486 and EA-I- RU 486 groups showed that the adrenal CORT content, and hippocampal GR mRNA expression level of the latter were remarkably lower than those of the former （P〈0.05）. Compared with the normal control group,the expression level of GR mRNA of the hipppocampal and pituitary tissues in the model ,constraint-stress,and RU 486 groups,and those of the hy- pothalamus in the constraint-stress and RU 486 groups were down-regulated significantly （P〈0.05）. In comparison with the constraint-stress group, hippocampal, hypothalamic and pituitary GR mRNA expression level in the EA group were upregulated considerably （P〈0.05）. No significant differences were found among model, Flu, constraint-stress, RU 486 and EA ＋ RU 486 groups in the ardenal CORT contents,and hippocampal,hypothalamic and pituitary GR mRNA expression levels （P〈0.05）. Conclusion EA can effectively dewn-regulate adrenal CORT content and hippcoampal GR mRNA expression and normalize the function of HPA axis negative feed reflex in the depression rats,which may contribute to its effect in relieving depression.