慢性应激肝郁模型大鼠蓝斑CRF、c-fos的表达及逍遥散的干预作用

The expression of CRF and c-fos in rat locus coeruleus under chronic stress and the therapeutic effect of Xiaoyao powder

目的观察慢性应激状态下大鼠一般状况,血清促肾上腺皮质激素释放激素(CRH)浓度,蓝斑(LC)中促肾上腺皮质激素释放因子(CRF)、即刻早期基因c-fos的表达,以及逍遥散对其的干预效应。方法将18只SD健康雄性大鼠随机分为正常对照、模型、逍遥散治疗组,每组6只。采用束缚的方法造模,观察大鼠行为、饮食、排便的变化;造模21d后取出蓝斑,用ELISA法检测血清中CRH浓度,Real-timePCR检测蓝斑中CRFmRNA和c-fosmRNA的表达。结果模型组大鼠行为、排便、饮食出现明显异常;与正常对照组比较,模型组大鼠血清CRH浓度升高,蓝斑中CRFmRNA和c-fosmRNA表达均上调(P<0.01);与模型组比较,逍遥散组大鼠血清CRH浓度下降,蓝斑中CRFmRNA和c-fosmRNA表达下调(P<0.01);逍遥散组较对照组CRH浓度升高、CRFmRNA和c-fosmRNA表达上调,但差异无统计学意义(P>0.05)。结论神经递质CRF介导了慢性束缚应激中LC的激活,转录因子c-fos亦参与了其调控,而逍遥散则可以有效地进行干预,下调其过表达。

Objective To observe the general condition of rats ,the serum corticotropin-releasing hormone （CRH） concentration, the expression of CRF and c-fos in the locus coeruleus （LC） under chronic stress, and to evaluate the therapeutic effect of Xiaoyao powder. Methods 18 healthy male SD rats were randomly divided into the control group, the model group,and the treatment （Xiaoyao powder） group （n=6）. The rat model was established by chronic stress method with immobilization. The behavior, diet, and feces were monitored. LC was isolated from brains on 21st day after modeling. The serum CRH concentration was determined by ELISA, and the mRNA levels of CRF and c-fos were analyzed by RT-PCR. Results The model group showed abnormality in behavior, feces, diet, and significant increase in the serum CRH concentration and the mRNA levels of CRF and c-los in the LC （P〈O.01） compared to the control group. In contrast, Xiaoyao powder-treated group exhibited significant decrease in the serum CRH concentration and the mRNA levels of CRF and c-fos （P〈0.01） compared to the model group whereas it displayed no significant difference when compared to the control group. Conclusion Neurotransmitter CRF mediated the activation of LC under chronic stress, and the transcription factor c-fos is also involved in this regulation, while Xiaoyao powder can effectively reverse this effect.