摘要目的 探讨广泛性焦虑症(generalized anxiety disorder,GAD)患者外周血单核细胞长链非编码RNA(long noncoding RNA,lncRNA)差异表达及治疗前后lncRNA表达水平的变化.方法 对GAD患者(患者组,n=80)和正常对照组( n=40)外周血单核细胞基因芯片筛查出的10种差异表达lncRNAs进行qRT-PCR验证;对26例GAD患者治疗前、治疗6周分别检测lncRNA表达水平和施测汉密尔顿焦虑量表(HAMA).结果 芯片筛查发现差异表达的10种 lncRNA经 PCR验证有6种[lncRNA4(7. 44± 2. 26)、lncRNA5 ( 6. 83 ± 2. 28)、 lncRNA6 ( 8. 09 ± 2. 30)、 lncRNA8 ( 9. 10 ± 2. 36)、lncRNA9(7. 66±2. 12)、lncRNA10(7. 34± 2. 12)]显著上调( Z=-3. 022~-1. 996,P<0. 05或0. 01).lncRNA4(9. 73 ± 2. 53)、lncRNA6 ( 9. 91 ± 2. 01)、 lncRNA8 ( 10. 48 ± 1. 68)、 lncRNA9 ( 9. 02 ± 1. 58)、lncRNA10(9. 04±2. 08)在治疗6 周后表达水平显著低于治疗前(Z=-3. 180~-2. 530,P<0. 05 或0. 01).经抗焦虑治疗6周后,GAD患者的焦虑总分[(11. 19±8. 37)分]、躯体性焦虑因子分[(5. 31± 4. 76)分]和精神性焦虑因子分[(5. 88±3. 82)分]均显著低于治疗前(t=5. 502~5. 971,P<0. 01).抗焦虑药治疗前后lncRNA4、lncRNA6、lncRNA8、lncRNA9、lncRNA10表达变化量与HAMA总分、精神性焦虑分值变化量显著正相关(r=0. 39~0. 69,P<0. 05或0. 01);lncRNA6、lncRNA8、lncRNA10表达变化量与躯体性焦虑分值变化量显著正相关(r=0. 44~0. 59,P<0. 01).结论 lncRNA4、lncRNA5、lncRNA6、lncRNA8、lncRNA9、lncRNA10在广泛性焦虑症患者中表达上调,抗焦虑治疗逆转lncRNA的表达水平,并与焦虑症改善程度密切关联.

abstractsObjective To confirm expression alteration of long non-coding RNA( lncRNA) in pe-ripheral blood mononuclear cells (PBMCs) of generalized anxiety disorder( GAD) patients and anti-anxiety treatment effects on aberrant expression of lncRNAs. Methods Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed in 80 GAD patients and 40 healthy participants to con-firm 10 aberrant lncRNAs screened by microarray expression profiling. And 26 out of all the 80 GAD patients were recruited for lncRNA expression level testing and Hamilton Anxiety Scale(HAMA) assessments before and after 6 weeks’ treatment. Results Six of ten lncRNAs selected by array profiling (lncRNA4(7. 44± 2. 26),lncRNA5(6. 83±2. 28),lncRNA6(8. 09±2. 30),lncRNA8(9. 10±2. 36),lncRNA9(7. 66±2. 12), lncRNA10(7. 34±2. 12)) were verified by qRT-PCR that the lncRNA expression levels were significantly up regulated in GAD patients compared with healthy controls ( Z=-3. 022--1. 996,P<0. 05 or 0. 01),and lncRNA4(9. 73 ± 2. 53),lncRNA6 ( 9. 91 ± 2. 01), lncRNA8 ( 10. 48 ± 1. 68), lncRNA9 ( 9. 02 ± 1. 58), lncRNA10(9. 04 ± 2. 08) were down regulated significantly after 6 weeks’ anti-anxiety treatment ( Z=-3. 180--2. 530,P<0. 05 or 0. 01) along with signicant reduction of total HAMA score (11. 19±8. 37),di-mension scores of somatic anxiety(5. 31±4. 76),psychic anxiety(5. 88±3. 82) (t=5. 502-5. 971,P<0. 01). The alterations of lncRNA4,lncRNA6,lncRNA8,lncRNA9,lncRNA10 were positively correlated with that of HAMA total score and psychic anxiety score(r=0. 39-0. 69,P<0. 05 or 0. 01),and alteration of lncRNA6, lncRNA8,lncRNA10 had positive correlation with that of somatic anxiety score(r=0. 44-0. 59,P<0. 01). Conclusion The expression level of lncRNA4,lncRNA5,lncRNA6,lncRNA8,lncRNA9,lncRNA10 are up-regulation in PBMCs of GAD patients and anti-anxiety treatment can reverse the expression level of lncRNAs. Alteration of lncRNA expression has osculatory association with improvement of anxious symptom.