帕罗西汀对慢性不可预见温和刺激的抑郁症大鼠抑郁行为的影响及其机制

Anti-depressant effect of paroxedine in rats with depression induced by chronic unpredicted mild stress

目的探讨帕罗西汀对慢性不可预见温和刺激(Chronic unpredicted mild stress,CUMS)的抑郁症大鼠抑郁行为的影响及其机制。方法将SD大鼠随机分为正常对照组(NG)、模型组(MG)、帕罗西汀模型组(PMG)及帕罗西汀对照组(PNG),MG组和PMG组采用孤养结合CUMS方式复制大鼠抑郁模型,每天PMG组和PNG组灌胃盐酸帕罗西汀1.8 mg/kg,NG组和MG组灌胃等体积的5%CMC-Na溶液。通过高架十字迷宫试验和糖水偏好试验评价大鼠的抑郁行为;采用常规生物化学方法测定大鼠大脑皮层丙二醛(Malonaldehyde,MDA)含量及超氧化物歧化酶(Superoxide dismutase,SOD)和过氧化氢酶(Catalase,CAT)活性;RT-PCR检测海马5-羟色胺转运体(5-Hydroxy-tryptamine transporter,5-HTT)和去甲肾上腺素转运体(Noradrenaline transporter,NET)基因mRNA的转录水平。结果与NG组相比,MG组大鼠进入开放臂的次数和停留时间显著减少(P<0.01或P<0.001),而在封闭臂停留的时间明显延长(P<0.01);糖水偏好百分率显著下降(P<0.001);大脑皮层MDA含量显著升高(P<0.01),SOD和CAT活性显著降低(P<0.05);海马5-HTT和脑桥NET基因mRNA的转录水平均显著降低(P<0.001)。帕罗西汀能明显抑制CUMS诱导的上述改变(P<0.05),而对正常大鼠无显著影响(P<0.05)。结论帕罗西汀能明显改善CUMS所致的大鼠抑郁行为,其机制与增强机体抗氧化应激能力、上调海马5-HTT和脑桥NET基因mRNA的转录水平有关。

Objective To investigate the anti-depressant effect of paroxedine in rats with depression induced by chronic unpredicted mild stress （CUMS） as well as the relevant mechanism. Methods Rats were randomly divided into normal control （NG）, model control （MG）, model ＋ paroxedine （PMG） and normal ＋ paroxedine （PNG） groups. Rat model of depression was copied by CUMS under solitary condition. The rats in PMG and PNG groups were treated with paroxedine hydrochloride at a dosage of 1.8 mg/ （kg · d） by gavage once a day, while those in NG and MG groups with 5% CMCNa solution at an equal volume. Elevated plus maze （EPM） and sucrose preference test （SPT） were used to evaluate the behaviors of rats. The malonyldialdehyde （MDA） level as well as superoxide dismutase （SOD） and eatalase （CAT） activi- ties in cortex were determined by routine biochemical methods. The transcription levels of 5-hydroxytryptamine transporter （5-HTF） mRNA in hippocampus and noradrenaline transporter （NET） mRNA in Pons were evaluated by RT-PCR. Resuits Compared with those in NG group, the time and number of entry into open arm in MG group decreased significantly （P 〈 0. 01 or P 〈 0. 001 ）, while the time of entry into closed arm was prolonged significantly （P 〈 0. 01 ）, the sucrose preference percentage decreased significantly （P 〈 0. 001 ）, the MDA level increased significantly （P 〈 0. 01 ）, the SOD and CAT activities decreased significantly （P 〈 0. 05）, and the transcription levels of 5-HTT and NET mRNAs decreased significantly （P 〈 0. 001 ）. Paroxedine blunted the change induced by CUMS significantly （P 〈 0. 05）, while showed no significant influence on normal rats （P 〉 0. 05）. Conclusion Paroxedine improved the depression syndromes of rats induced by CUMS, of which the mechanism involved the enhancement of anti-oxidative stress ability and upregulation of 5-HTF and NET mRNA transcriptions.