组蛋白乙酰化调控异常与大鼠抑郁行为的关系研究

Research on relationship between abnormal regulation of histone acetylation and depression in rats

目的研究组蛋白乙酰化与慢性不可预见刺激(chronic unpredictable stress,CUS)致大鼠抑郁行为的关系。方法30只♂Sprague Dawley(SD)大鼠随机分为对照组和模型组,采用孤养结合CUS方式连续刺激28 d建立大鼠抑郁症模型;以开场实验和强迫游泳实验评价大鼠抑郁行为;采用实时荧光定量PCR法检测大鼠前脑皮层和海马组蛋白去乙酰化酶2(histone deacetylase 2,HDAC2)mRNA表达;采用Western blot法检测大鼠前脑皮层和海马组蛋白H3(histone3,H3)、组蛋白H4(histone 4,H4)、乙酰化组蛋白H3(actylation-histone 3,ac H3)及乙酰化组蛋白H4(actylation-histone4,ac H4)蛋白表达水平。结果与对照组大鼠相比,模型组大鼠开场实验得分明显降低(P<0.01)、强迫游泳实验不动时间明显延长(P<0.01)、前脑皮层和海马HDAC2 mRNA和蛋白表达明显增加(P<0.01)、组蛋白H3和组蛋白H4蛋白表达均无明显差异、ac H3及ac H4蛋白水平均明显降低(P<0.01)。结论 CUS诱导大鼠产生抑郁样行为改变,其机制可能与脑内HDAC表达增高致组蛋白乙酰化修饰水平降低有关。

Aim To study the role of histone acetylation and its involvement in the depression-like behaviors of rats induced by chronic unpredictable stress（ CUS）. Methods Thirty male Sprague Dawley（ SD） rats were randomly divided into control group and model group. The method of solitary condition with CUS for consecutive 28 days was used to establish the rat depression model. The open-field test（ OFT） and the forced swimming test（ FST） were used to evaluate the depressive behaviors of rats; the real time PCR wasused to detect the change of HDAC2 mRNA, and Western blot was used to determine the protein expressions of H3,H4,ac H3 and ac H4 in the prefrontal cortex and hippocampus of rats. Results Model group showed obvious depression-like behaviors with decreasing locomotive activity in OFT（ P 0. 01） and increasing immobility time in FST（ P 0. 01）,up-regulating the mRNA and protein expression of HDAC2（ P 0. 01）,and down-regulating the protein expression of ac H3 and ac H4（ P 0. 01） in the prefrontal cortexand hippocampus significantly,compared with control group. Conclusion The mechanism of depressive behaviors of rats induced by CUS may be associated with down-regulating the level of histone acetylation modification.