电针对慢性应激抑郁模型大鼠海马及血清caspase-12表达的影响

目的观察c-jun氨基末端激酶(JNK)信号转导通路阻断下电针对慢性应激抑郁模型大鼠海马及血清半胱氨酸天冬氨酸蛋白酶-12(caspase-12)表达的影响,探讨针刺抗抑郁的作用机制。方法 SD大鼠随机分为空白组、模型组、针刺组、氟西汀组、模型+二甲基亚砜(DMSO)组、模型+JNK通路阻断剂SP600125(以下简称SP)组、针刺+SP组、氟西汀+SP组,每组9只。除空白组外,其余组均采用慢性应激结合孤养的方法造模。电针干预选取"内关""三阴交"穴,每次20 min,每天1次,治疗21 d;阳性对照药物给予氟西汀5 mg/kg灌胃,治疗21 d。通过旷场实验对大鼠进行行为学评价,采用酶联免疫吸附(ELISA)法检测大鼠海马和血清中caspase-12蛋白表达。结果实验前各组大鼠行为学检测均无统计学差异(P0.05)。实验第21天,与空白组相比,模型组的水平穿越格数、竖立次数明显降低(P0.01);与模型组相比,针刺组能提高模型大鼠的水平穿越格数(P0.05)。与空白组比较,模型组大鼠海马caspase-12蛋白表达明显上升(P0.01);与模型组比较,模型+DMSO组、氟西汀组、氟西汀+SP组、模型+SP组、针刺组、针刺+SP组大鼠海马caspase-12蛋白表达均下降(P0.05)。与空白组比较,模型组大鼠血清caspase-12蛋白表达降低;与模型组比较,模型+DMSO组、模型+SP组、氟西汀组、针刺+SP组大鼠血清caspase-12蛋白表达降低,而氟西汀+SP组、针刺组大鼠caspase-12表达升高,但差异均没有统计学意义(P0.05)。结论针刺可能是通过抑制JNK信号转导通路活性,从而降低慢性应激模型大鼠海马caspase-12蛋白表达,减少海马神经元凋亡,从而发挥抗抑郁效应。

Effects of electroacupuncture on the expression of caspase-12 in hippo-campus and serum of rats with chronic unpredictable mild stress

Objective To observe the effects of electroacupuncture(EA)on the expression of central and peripheral cysteine aspartic acid protease-12 via JNK signal transduction pathway in rats with chronic stress depression and to explore anti-depression mechanism of electro-acupuncture.Methods SD rats were randomly divided into blank group,stress model group,acupuncture group,fluoxetine group,model+DMSO(dimethyl sulfoxide,soluble organic solvent)group, model+JNK pathway blocker SP600125 (hereinafter abbreviated as SP)group, acupuncture +SP group, and fluoxetine +SP group(n=9 in each group).The combination of chronic stress and solitary raising was used to establish chronic unpre-dictable mild stress model in seven groups except the control group.The investigated intervention was EA at"Neiguan(PC6)"and"Sanyinjiao(SP6)"points,20 min for each session,once a day,for 21 con-secutive days.The positive control group was treated with fluoxetine 5 mg/kg by oral gavage for 21 days. Open field test was used to observe the rats' behaviors.The expression of caspase-12 protein in hippo-campus and serum was measured by using ELISA.Results Before the experiment,there was no statistic difference in rat behaviors of all groups(P>0.05).At Day 21 of the experiment,the horizontal crossing lattice and frequency of vertical movements markedly decreased compared to the blank group(P <0.01).Compared with the model group,EA increased the horizontal crossing lattice(P<0.05).Com-pared with the blank group,the expression of caspase-12 protein in the model group increased significant-ly(P<0.01).Compared with the model group, the expression of caspase-12 protein in the model +DMSO group,fluoxetine group,fluoxetine+SP group,acupuncture group and SP group all decreased(P<0.05).Compared with the blank group,the expression of caspase-12 protein in the model group de-creased.Compared with the model group, the expression of caspase-12 protein in the model +DMSO group,model+SP group, fluoxetine group and acupuncture +SP group(P>0.05)decreased, while the expression of caspase-12 in fluoxetine+SP group and acupuncture group was higher than that in the control group,but all the differences were not statistically significant(P>0.05).Conclusion Acu-puncture treatment may reduce the expression of caspase-12 protein in the hippocampus of chronic stress rats by effectively inhibiting the JNK signal transduction pathway activity and reducing the apoptosis of hippocampal neuron,which contributes to its anti-depression mechanism.