CUMS所致大鼠抑郁行为的性别差异与HPA轴功能及BDNF表达相关性研究

Study on the correlation between the gender difference in depressive behavior of rats induced by CUMS and function of HPA axis and BDNF expression

目的探讨慢性轻度不可预见性刺激(CUMS)所致大鼠抑郁行为性别差异与下丘脑-垂体-肾上腺皮质轴(HPA)及脑源性神经营养因子(BDNF)表达的相关性。方法选择雌雄各半的远交群SD大鼠64只,以随机数字表格法为分配依据分雌性对照组、雄性对照组、雌性模型组以及雄性模型组,每组16只。应用CUMS以及孤养模式来建立大鼠抑郁模型。应用糖水消耗及高架迷宫法评估大鼠抑郁行为程度,应用Western-blot法检测下丘脑促肾上腺皮质激素释放因子(CRF)mRNA蛋白表达及转录水平,应用荧光定量PCR法检测大鼠海马BDNF mRNA蛋白表达及转录水平,应用放射免疫法检测大鼠血清皮质酮(CORT)含量。结果雌性模型组与雄性模型组高架迷宫开放臂次数、开放臂停留时间、糖水偏爱率、向下探究次数均显著少于雌性对照组与雄性对照组(P均<0.05),血清CORT含量、下丘脑CRF mRNA蛋白表达及转录水平均明显高于雌性对照组与雄性对照组(P均<0.05),而大鼠海马BDNF mRNA蛋白表达及转录水平则明显低于雌性对照组与雄性对照组(P均<0.05)。雄性模型组大鼠进入高架迷宫开放臂与关闭臂次数、中央停留时间、糖水偏爱率、向下探究次数、血清CORT含量、下丘脑CRF mRNA蛋白表达及转录水平明显低于雌性模型组(P均<0.05),但关闭臂停留时间显著长于雌性模型组(P<0.05)。结论 CUMS所致大鼠抑郁行为的性别差异与HPA轴功能及BDNF表达有密切关系,可为抑郁症的防治及机制研究提供有力实验依据。

Objective It is to investigate the correlation between the gender differences in depressive behavior of rats induced by CUMS and hypothalamic pituitary adrenal axis（ HPA） and brain derived neurotrophic factor（ BDNF） expression.Methods 64 case of each half of the male and female of outbred group SD rats were selected,and divided into 4 groups by using random number table method as female control group,male control group,female model group and male model group with16 rats in each group. The rat model of depression was built by CUMS and isolated feed mode. The degree of the depressive behavior of rats was valued by sugar consumption and elevated maze method. The protein expression and transcription level of corticotrophin releasing factor（ CRF） mRNA in hypothalamus were detected by Western-blot method. The protein expression and transcription level of Brain- Derived Neurotrophic Factor（ BDNF） mRNA in hippocampus were detected by fluorescence quantitative PCR. The content of serum corticosterone（ CORT） of rats was detected by radioimmunoassay. Results The number of into open arm,residence time in opened arm,sucrose preference rate and times of down inquiry of male and female model groups were significantly decreased than that of female and male control group（ all P 〈0. 05）; and the content of serum CORT and hypothalamus CRF protein expression and transcription level of mRNA were increased significantly than that of female and male control groups（ all P 〈0. 05）; while the rat hippocampus BDNF protein expression and transcription level of mRNA were significantly decreased than that of female and male control groups（ all P 〈0. 05）. The times of into elevated maze opened arm and closed arm,the central residence time,sucrose preference rate,times of down inquiry,serum CORT content,hypothalamus CRF protein expression and transcription level of mRNA in male model group were significantly lower than that in female model group（ all P 〈0. 05）; but the closed arm retention time was significantly longer than that in female model group（ P 〈0. 05）. Conclusion The gender differences in depressive behavior of rats induced by CUMS have close relationship with the expression of HPA and BDNF axis function; it can provide strong experimental evidence for the prevention and cure and study of mechanism of depression.