逍遥散对慢性应激大鼠下丘脑-垂体-肾上腺轴调控作用机制的初步研究

Primary research on the mechanisms of Xiaoyao powder influences hypothalamus-pituitary-adrenal axis of chronic stress rats

目的 观测逍遥散对慢性应激损伤大鼠海马对下丘脑-垂体-肾上腺（HPA）轴调控的变化,探讨逍遥散抗应激损伤的神经内分泌变化.方法 以慢性多相性应激大鼠为研究对象,动物分组采用随机数字表法;RU-38486为工具药;酶联免疫吸附法检测大鼠血清皮质酮（CORT）;荧光免疫组化方法 检测大鼠海马神经元内糖皮质激素受体（GR）.结果 与空白对照组（1.09±0.11;0.57±0.10）相比较,模型组大鼠海马神经元内GR表达明显减少（0.65±0.10;P＜0.01）,促肾上腺皮质激素释放激素（CRH）mRNA表达明显升高（1.12±0.11;P＜0.01）,RU-38486组大鼠海马神经元内GR表达明显增加（1.59±0.11;P＜0.01）,CRH mRNA表达明显减少（0.48±0.10;P＜0.05）.而逍遥散组大鼠海马神经元内GR及下丘脑CRH mRNA表达均无统计学差异（0.62±0.08;0.97±0.13;P＞0.05）;与模型组比较,RU-38486及逍遥散干预大鼠海马神经元内GR表达均明显增加（P＜0.01）,下丘脑CRH mRNA表达均明显降低（P＜0.01）.结论 慢性应激可导致大鼠海马神经元内GR表达减少,下丘脑CRH mRNA表达升高,而逍遥散能抑制这种因慢性应激所致的海马神经元内GR及下丘脑神经元内CRH mRNA的表达变化,这可能是逍遥散调控慢性应激状态下HPA轴的兴奋性以达到抗应激损伤的关键机制.

Objective To observe the mechanisms that Xiaoyao powder influences the hypothalamus-pituitary-adrenal （HPA） axis of chronic-stress rats. Methods Chronic stress rats were as researching object,and RU-38486 acted as tool drugs. The serum-GC density of rats were tested with ELISA,and the glucocortcoid（GR） in hippocampus neuron were tested with immunofluorescence,the CRH mRNA in hypothalamus were tested by in situ hybridization （ISH）. Results Compared with normal group （ 1.09 ± 0.11 ;0.57 ± 0.10）, the expression of GR in hippocampus of model group decreased（0.65 ± 0. 10; P ＜ 0. 01 ）, and the expression of CRH mRNA in hypothalamus of model group increased （ 1.12 ±0. 11; P＜0. 0l ） ,the GR in hippocampus of RU-38486 group increased （ 1.59 ± 0. 11; P ＜ 0. 01 ）, and the expression of CRH mRNA in hypothalamus of RU-38486 group reduced （0.48±0.10; P＜0.05） ,but both the expression of GR in hippocampus and the CRH mRNA in hypothalamus of Xiaoyao powder group were no change （0.62 ±0.08;0.97 ±0.13; P＞0.05）. Compared with model group,both the expression of GR in hippocampus of RU-38486 and Xiaoyao powder group increased （P＜0. 01） ,and both the expression of CRH mRNA in hypothalamus of RU-38486 and Xiaoyao powder group reduced （P＜0.01）. Conclusion Multi-stress can result in the expression of GR in hippocampus of rats decreasing and the expression of CRH mRNA in hypothalamus increasing, but those changes can be restrained by Xiaoyao powder, and it is the maybe mechanism of Xiaoyao Powder resisting chronic stress in HPA axis.