中华精神科杂志
中華精神科雜誌
중화정신과잡지
CHINESE JOURNA OF PSYCHIATRY
2011年
3期
169-174
,共6页
郭晓云%崔东红%傅迎美%俞瑾%吴根诚%江三多%翁史旻%张燃%江开达
郭曉雲%崔東紅%傅迎美%俞瑾%吳根誠%江三多%翁史旻%張燃%江開達
곽효운%최동홍%부영미%유근%오근성%강삼다%옹사민%장연%강개체
寡核苷酸序列分析%海马%基因%应激%文拉法辛
寡覈苷痠序列分析%海馬%基因%應激%文拉法辛
과핵감산서렬분석%해마%기인%응격%문랍법신
Oligonucleotide array sequence analysis%Hippocampus%Genes%Stress%Venlafaxine
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.
目的 採用基因芯片技術篩選文拉法辛作用相關基因.方法 按照隨機數字錶法將18隻大鼠分為正常對照組、文拉法辛+應激組和生理鹽水+應激組,每組各6隻.正常對照組除特彆說明外,不進行任何榦預;應激組採用慢性輕度應激法製造抑鬱癥大鼠模型;實驗第5～8週,對應激組分彆給予文拉法辛[2.5 mg/(kg·d)]和生理鹽水榦預.每週進行體質量和糖水攝入量測定.第8週末處死大鼠,按照隨機數字錶隨機取3隻文拉法辛+應激組大鼠和所有生理鹽水+應激組大鼠雙側海馬,提取總RNA,在反轉錄eDNA時,分彆用Cy3、Cy5 2種激髮波長熒光標記,穫得2組樣本cDNA探針.將2組探針混閤後與大鼠10 891條全基因組cDNA芯片雜交,掃描併分析雜交結果.結果 (1)實驗第1～8週,正常對照組體質量[(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]明顯高于文拉法辛+應激組[(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]和生理鹽水+應激組[(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],差異均有統計學意義(P=0.000);實驗第4週,正常對照組糖水攝入量[(7.7±1.1)g]高于文拉法辛+應激組[(5.0±2.5)g]和生理鹽水+應激組[(4.9±2.5)g],差異有統計學意義(P=0.046,P=0.038);實驗第6～8週,文拉法辛+應激組糖水攝入量分彆為(9.4±5.2)、(17.9±5.9)、(18.9±5.5)g,與正常對照組[(13.4±2.1)、(15.8±3.8)、(15.7±4.4)g]比較,差異無統計學意義(P>0.05),但2組均高于生理鹽水+應激組[(5.3±4.3)、(4.9±3.9)、(4.7±2.9)g],差異有統計學意義(P=0.013,P=0.000,P:0.000).(2)噹Cy5與Cy3比值≥2或≤0.5時,3張芯片中有10條基因在文拉法辛組中均上調錶達.結論 文拉法辛的作用機製可能與神經髮育、神經可塑性、離子通道及跨膜轉運體蛋白基因相關.
목적 채용기인심편기술사선문랍법신작용상관기인.방법 안조수궤수자표법장18지대서분위정상대조조、문랍법신+응격조화생리염수+응격조,매조각6지.정상대조조제특별설명외,불진행임하간예;응격조채용만성경도응격법제조억욱증대서모형;실험제5～8주,대응격조분별급여문랍법신[2.5 mg/(kg·d)]화생리염수간예.매주진행체질량화당수섭입량측정.제8주말처사대서,안조수궤수자표수궤취3지문랍법신+응격조대서화소유생리염수+응격조대서쌍측해마,제취총RNA,재반전록eDNA시,분별용Cy3、Cy5 2충격발파장형광표기,획득2조양본cDNA탐침.장2조탐침혼합후여대서10 891조전기인조cDNA심편잡교,소묘병분석잡교결과.결과 (1)실험제1～8주,정상대조조체질량[(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]명현고우문랍법신+응격조[(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]화생리염수+응격조[(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],차이균유통계학의의(P=0.000);실험제4주,정상대조조당수섭입량[(7.7±1.1)g]고우문랍법신+응격조[(5.0±2.5)g]화생리염수+응격조[(4.9±2.5)g],차이유통계학의의(P=0.046,P=0.038);실험제6～8주,문랍법신+응격조당수섭입량분별위(9.4±5.2)、(17.9±5.9)、(18.9±5.5)g,여정상대조조[(13.4±2.1)、(15.8±3.8)、(15.7±4.4)g]비교,차이무통계학의의(P>0.05),단2조균고우생리염수+응격조[(5.3±4.3)、(4.9±3.9)、(4.7±2.9)g],차이유통계학의의(P=0.013,P=0.000,P:0.000).(2)당Cy5여Cy3비치≥2혹≤0.5시,3장심편중유10조기인재문랍법신조중균상조표체.결론 문랍법신적작용궤제가능여신경발육、신경가소성、리자통도급과막전운체단백기인상관.
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.
