抑郁模型大鼠脑脊液miR-16与中缝核miR-16、5-羟色胺转运体表达的关联性研究

目的研究抑郁模型大鼠脑脊液miR-16是否能反映中缝核miR-16水平的变化,并与中缝核5-羟色胺转运体(serotonin transporter,SERT)的表达相关。方法将20只SD大鼠随机分为抑郁模型组和对照组,每组各10只。抑郁模型组大鼠接受21 d不可预知温和应激的刺激,对照组大鼠正常饲养。收集大鼠脑脊液测定miR-16,分离中缝核测定miR-16和SERT蛋白。比较模型组与对照组脑脊液miR-16、中缝核miR-16、SERT表达差异并分析三者的关联性。结果模型组大鼠脑脊液miR-16水平(0.19±0.10)和中缝核miR-16水平(0.65±0.22)均低于相应的对照组(0.35±0.12、0.84±0.18)(P0.01),中缝核SERT水平(0.99±0.29)高于对照组(0.59±0.18)(P=0.002)。脑脊液miR-16与中缝核miR-16呈显著正相关关系(r=0.95,P=0.000),而且脑脊液miR-16与中缝核miR-16一样,与中缝核SERT呈显著负相关(r=-0.91,P=0.000)。结论抑郁模型大鼠脑脊液miR-16水平能反映中缝核miR-16水平,并与中缝核SERT表达相关,可能可作为抑郁症的生物标记物。

Correlation between cerebrospinal fluid miR-16 and expression of miR-16 and serotonin transporters in the raphe of rats with depression model

Objective To investigate whether miR-16 in cerebrospinal fluid of rats with depression model can reflect the change of miR-16 level in the raphe and is related to the expression of serotonin transporter(SERT).Methods A total of 20 SD rats were randomly divided into depression model group and control group,with 10 rats in each group.Rats in the depression model group received 21 days of unpredictable mild stress stimulation,and the rats in the con-trol group were normally reared.The rat cerebrospinal fluid was collected for the determination of miR-16,and the raphe was isolated for the determination of miR-16 and SERT proteins.The expression difference of cerebrospinal fluid miR-16,raphe miR-16 and SERT were compared between the model group and the control group,and the correlation among the three indexes was analyzed.Results The levels of cerebrospinal fluid miR-16(0.19±0.10)and raphe miR-16(0.65±0.22)in the model group were lower than those of the corresponding control group(0.35±0.12,0.84±0.18)(P<0.01).The raphe SERT level(0.99±0.29)in the model group was higher than that of the control group(0.59±0.18)(P=0.002).There was a significant positive correlation between cerebrospinal fluid miR-16 and raphe miR-16(r=0.95,P=0.000),and cerebrospinal fluid miR-16 had the same negative correlation with the middle nucleus SERT as the raphe miR-16(r=-0.91,P=0.000).Conclusion The cerebrospinal fluid miR-16 in depression model rats can reflect the level of miR-16 in raphe and is related to the expression of SERT in raphe.It may be a biomarker of depression.