芪白平肺胶囊对COPD合并抑郁大鼠海马组织5-HT1AR、DA-1、DA-5表达的影响

Effects of Qibai Pingfei Capsules on Up-regulating Expression of 5-HT1AR mRNA,DA-1 and DA-5 in Hippocampus of Rat Model with COPD Accompanied with Depression

【目的】观察芪白平肺胶囊对慢性阻塞性肺疾病(COPD)合并抑郁大鼠海马组织中的单胺类神经递质5-羟色胺1A受体(5-HT1AR)及多巴胺(DA)亚型受体DA-1、DA-5表达的影响,探讨芪白平肺胶囊的干预机制。【方法】将90只Wistar雄性大鼠随机分为正常组、COPD合并抑郁组、芪白平肺胶囊组、文拉法辛组、芪白平肺胶囊+文拉法辛组。采用烟熏、断食、断水、游泳、水平摇晃、夹尾巴等方法,复制COPD合并抑郁大鼠模型。观察芪白平肺胶囊对COPD合并抑郁大鼠肺功能和一般表征的影响;采用实时定量逆转录—聚合酶链反应(RT-q PCR)测定大脑海马区5-HT1AR mRNA的转录水平,Western blot法检测海马区DA-1、DA-5受体蛋白表达。【结果】COPD合并抑郁组大鼠第0.3秒用力呼气容量(FEV0.3)、用力肺活量(FVC)和FEV0.3/FVC等肺功能参数值较正常组显著下降(P<0.01),芪白平肺胶囊组、芪白平肺胶囊+文拉法辛组和文拉法辛组的肺功能参数值较COPD合并抑郁组均有不同程度的上升(P<0.01)。与正常组比较,COPD合并抑郁组大鼠大脑海马区5-HT1AR mRNA及DA-1、DA-5蛋白表达水平显著降低(P<0.05)。芪白平肺胶囊组、文拉法辛组和芪白平肺胶囊+文拉法辛组也存在大脑海马区5-HT1AR mRNA转录水平及DA-1、DA-5蛋白表达的降低,但程度较轻。与COPD合并抑郁组比较,芪白平肺胶囊组、文拉法辛组和芪白平肺胶囊+文拉法辛组的5-HT1AR mRNA转录水平和DA-1、DA-5受体蛋白表达量显著增加(均P<0.05)。【结论】芪白平肺胶囊可提高COPD合并抑郁大鼠大脑神经递质5-HT1AR mRNA转录水平和DA-1、DA-5蛋白的含量。

Objective To investigate the effects of Qibai Pingfei Capsules（QPC）on the expression of monoamine neurotransmitters of 5-hydroxytryptamine receptor（5-HT） and dopamine（DA） receptors of DA1 and DA5 in the rats with chronic obstructive pulmonary disease（COPD） accompanied with depression, and to explore the possible therapeutic mechanism. Methods Ninety male Wistar rats were randomly divided into 6 groups,namely normal group,COPD depression group,QPC group,Venlafaxine group,and QPC plus Venlafaxine group. The rat model of COPD accompanied with depression was established by compound methods of smoking, fooddeprivation,water deprivation,forced swimming,shaking,and clipping tail. And then the effects of QPC on the lung function and the general characteristics were observed. Furthermore,the mRNA level of 5-HT1AR was determined by real-time quantitative reverse transcription PCR（RT-q PCR）,and protein levels of DA-1 and DA-5 in rat hippocampus were assayed by Western blot analysis. Results Compared with the normal group,forced expiratory volume in 0.3 second（FEV0.3）,the forced volume capacity（FVC） and FEV0.3/FVC in the COPD depression group were significantly reduced（P〈 0.01）. Compared with the COPD depression group,the values mentioned above were restored to different extents in the groups of QPC, Venlafaxine, and QPC plus Venlafaxine（P 〈0.01）. Compared with the normal group,the expression levels of 5-HT1AR mRNA,and DA-1 and DA-5 protein in the COPD depression group were significantly down-regulated, and their levels were also slightly decreased in the treatment groups（P 〈0.05）. Compared with the COPD depression group,the expression levels were up-regulated to various degrees in all of the treatment groups（P〈 0.05）. Conclusion QPC can increase the mRNA levels of 5-HT1AR and protein levels of DA-1 and DA-5 in the hippocampus of COPD with depression.