Objective To used microarray analysis to screen the related genes of venlafaxine. Methods All rats were divided into 3 groups (6 rats per group) according to the table of random digit, i. e. , normal control, venlafaxine + stress, saline + stress. The rats of normal control group receive no intervention until otherwise noted. The stress group was subjected to the chronic mild stress procedure for 8 weeks. Rats in stress group were interfered with venlafaxine [(2. 5 mg/(kg · d)]and saline in weeks 5-8. Weight and sucrose intake were tested every week. At the end of weeks 8, all rats were sacrificed. Three rats in venlafaxine group were randomly chosen. Hippocampus of both sides from chosen venlafaxine group and saline group were collected and total RNA was abstracted. The cDNA probes of venlafaxine and saline control were prepared by labeling cell RNA with Cy5 and Cy3 with reverse transcription respectively. The microarrays with 10 891 genes were hybridized against the cDNA probe mixture, and the fluorescent signals were scanned. Results From weeks 1 to 8, the weights in normal control group [(365.4 ±22.5) ,(383. 1 ± 17. 2), (434. 1 ± 35. 7), (467. 0 ± 30. 3), (496. 2 ±34.4),(516. 2 ± 34. 4) , (534. 8 ± 44.4) , (535. 5 ± 35. 7) g] were significantly higher than that in venlafaxine +stress [(322. 3 ±9.5), (335. 6±13. 8), (348. 8 ± 18.9), (370.0 ±22. 6), (391.2 ±31. 2), (394.0 ±24.4),(401.6 ±26.9),(409.2 ±29.9) g]and saline + stress groups [(313.2 ± 14.5), (328.2 ±11. 1) ,(350. 9 ± 15. 6) ,(345. 3 ±29. 0), (370. 8 ±42. 9), (396. 0 ±45. 8), (395. 0 ±49. 2), (404. 5 ±38. 6) g, P = 0. 000]. In weeks 4, the level of sucrose intake in normal control group [(7. 7 ± 1. 1) g] was higher than that in venlafaxine + stress [(5. 0 ± 2. 5) g, P = 0. 046] and saline + stress groups [(4. 9 ±2.5) g, P = 0. 038]. From weeks 6 there was no difference on sucrose intake between venlafaxine + stress [(9. 4±5.2), (17.9 ±5.9), (18.9 ±5.5) g] and normal control groups [(13.4 ±2. 1), (15. 8 ±3. 8),(15. 7 ± 4. 4) g,P>0. 05] , both of which were higher than saline + stress group [(5. 3 ± 4. 3) , (4. 9 ±3. 9) , (4.7 ±2.9) g, P =0. 013,0. 000,0. 000]. Ten genes were up-regulated in all venlafaxine treated rats when the ratio of Cy5 /Cy3 signal was ≥ 2. 0 or ≤0. 5. Conclusions The mechanism of venlafaxine treatment related to many genes, which include neural development, neural plastically, ion channel, and transmembrane transporters.%目的 采用基因芯片技术筛选文拉法辛作用相关基因.方法 按照随机数字表法将18只大鼠分为正常对照组、文拉法辛+应激组和生理盐水+应激组,每组各6只.正常对照组除特别说明外,不进行任何干预;应激组采用慢性轻度应激法制造抑郁症大鼠模型;实验第5～8周,对应激组分别给予文拉法辛[2.5 mg/(kg·d)]和生理盐水干预.每周进行体质量和糖水摄入量测定.第8周末处死大鼠,按照随机数字表随机取3只文拉法辛+应激组大鼠和所有生理盐水+应激组大鼠双侧海马,提取总RNA,在反转录eDNA时,分别用Cy3、Cy5 2种激发波长荧光标记,获得2组样本cDNA探针.将2组探针混合后与大鼠10 891条全基因组cDNA芯片杂交,扫描并分析杂交结果.结果 (1)实验第1～8周,正常对照组体质量[(365.4±22.5)、(383.1±17.2)、(434.1±35.7)、(467.0±30.3)、(496.2±34.4)、(516.2±34.4)、(534.8±44.4)、(535.5±35.7)g]明显高于文拉法辛+应激组[(322.3±9.5)、(335.6±13.8)、(348.8±18.9)、(370.0±22.6)、(391.2±31.2)、(394.0±24.4)、(401.6±26.9)、(409.2±29.9)g]和生理盐水+应激组[(313.2±14.5)、(328.2±11.1)、(350.9±15.6)、(345.3±29.0)、(370.8±42.9)、(396.0±45.8)、(395.0±49.2)、(404.5±38.6)g],差异均有统计学意义(P=0.000);实验第4周,正常对照组糖水摄入量[(7.7±1.1)g]高于文拉法辛+应激组[(5.0±2.5)g]和生理盐水+应激组[(4.9±2.5)g],差异有统计学意义(P=0.046,P=0.038);实验第6～8周,文拉法辛+应激组糖水摄入量分别为(9.4±5.2)、(17.9±5.9)、(18.9±5.5)g,与正常对照组[(13.4±2.1)、(15.8±3.8)、(15.7±4.4)g]比较,差异无统计学意义(P>0.05),但2组均高于生理盐水+应激组[(5.3±4.3)、(4.9±3.9)、(4.7±2.9)g],差异有统计学意义(P=0.013,P=0.000,P:0.000).(2)当Cy5与Cy3比值≥2或≤0.5时,3张芯片中有10条基因在文拉法辛组中均上调表达.结论 文拉法辛的作用机制可能与神经发育、神经可塑性、离子通道及跨膜转运体蛋白基因相关.
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