中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2014年
6期
848-852
,共5页
胡小娅%费慧芝%蒋心惠%刘丹%邱红梅%周岐新
鬍小婭%費慧芝%蔣心惠%劉丹%邱紅梅%週岐新
호소아%비혜지%장심혜%류단%구홍매%주기신
文拉法辛%抑郁症%慢性不可预见刺激%强迫游泳%氧化应激%5-HTT%NET
文拉法辛%抑鬱癥%慢性不可預見刺激%彊迫遊泳%氧化應激%5-HTT%NET
문랍법신%억욱증%만성불가예견자격%강박유영%양화응격%5-HTT%NET
venlafaxine%depression%CUS%force swim-ming%oxidative stress%5-HTT%NET
目的:探讨文拉法辛抗慢性不可预见刺激所致大鼠抑郁症作用与氧化应激和海马去甲肾上腺素转运体( norepi-nephrine transporter,NET)、5羟色胺转运体(serotonin trans-porter,5-HTT)表达的关系。方法裔SD大鼠80只,根据开场实验得分分为4组,即正常对照组( NG)、模型组( MG)、文拉法辛处理的正常对照组( VNG)和文拉法辛处理的模型组( VMG)。采用孤养结合慢性不可预见刺激( chronic unpre-dictable stress,CUS)方法建立大鼠抑郁模型;给药组每天给予文拉法辛(23.4 mg·kg-1·d-1),NG和MG组每天给予同体积溶剂。采用强迫游泳( force swimming)实验评价大鼠的抑郁行为,生物化学方法检测大鼠血清的超氧化物岐化酶( superoxide dismutase,SOD)活性与丙二醛( malondialdehyde, MDA)含量,实时定量RT-PCR分析海马5-HTT、NET的mR-NA表达, Western blot 测定海马5-HTT、NET 的蛋白表达。结果相对于NG组,MG组大鼠在强迫游泳实验中的不动时间明显增加,SOD活性降低,血清MDA含量升高,海马5-HTT表达明显下降,而NET的表达明显升高。文拉法辛干预能阻遏CUMS诱导的上述变化;文拉法辛处理对正常对照大鼠的行为、SOD、MDA和5-HTT及NET表达无明显影响。结论文拉法辛抑制CUS诱导大鼠出现焦虑抑郁样行为的机制至少部分与其改善脑内氧化应激平衡,逆转5-HTT和NET异常表达有关。
目的:探討文拉法辛抗慢性不可預見刺激所緻大鼠抑鬱癥作用與氧化應激和海馬去甲腎上腺素轉運體( norepi-nephrine transporter,NET)、5羥色胺轉運體(serotonin trans-porter,5-HTT)錶達的關繫。方法裔SD大鼠80隻,根據開場實驗得分分為4組,即正常對照組( NG)、模型組( MG)、文拉法辛處理的正常對照組( VNG)和文拉法辛處理的模型組( VMG)。採用孤養結閤慢性不可預見刺激( chronic unpre-dictable stress,CUS)方法建立大鼠抑鬱模型;給藥組每天給予文拉法辛(23.4 mg·kg-1·d-1),NG和MG組每天給予同體積溶劑。採用彊迫遊泳( force swimming)實驗評價大鼠的抑鬱行為,生物化學方法檢測大鼠血清的超氧化物岐化酶( superoxide dismutase,SOD)活性與丙二醛( malondialdehyde, MDA)含量,實時定量RT-PCR分析海馬5-HTT、NET的mR-NA錶達, Western blot 測定海馬5-HTT、NET 的蛋白錶達。結果相對于NG組,MG組大鼠在彊迫遊泳實驗中的不動時間明顯增加,SOD活性降低,血清MDA含量升高,海馬5-HTT錶達明顯下降,而NET的錶達明顯升高。文拉法辛榦預能阻遏CUMS誘導的上述變化;文拉法辛處理對正常對照大鼠的行為、SOD、MDA和5-HTT及NET錶達無明顯影響。結論文拉法辛抑製CUS誘導大鼠齣現焦慮抑鬱樣行為的機製至少部分與其改善腦內氧化應激平衡,逆轉5-HTT和NET異常錶達有關。
목적:탐토문랍법신항만성불가예견자격소치대서억욱증작용여양화응격화해마거갑신상선소전운체( norepi-nephrine transporter,NET)、5간색알전운체(serotonin trans-porter,5-HTT)표체적관계。방법예SD대서80지,근거개장실험득분분위4조,즉정상대조조( NG)、모형조( MG)、문랍법신처리적정상대조조( VNG)화문랍법신처리적모형조( VMG)。채용고양결합만성불가예견자격( chronic unpre-dictable stress,CUS)방법건립대서억욱모형;급약조매천급여문랍법신(23.4 mg·kg-1·d-1),NG화MG조매천급여동체적용제。채용강박유영( force swimming)실험평개대서적억욱행위,생물화학방법검측대서혈청적초양화물기화매( superoxide dismutase,SOD)활성여병이철( malondialdehyde, MDA)함량,실시정량RT-PCR분석해마5-HTT、NET적mR-NA표체, Western blot 측정해마5-HTT、NET 적단백표체。결과상대우NG조,MG조대서재강박유영실험중적불동시간명현증가,SOD활성강저,혈청MDA함량승고,해마5-HTT표체명현하강,이NET적표체명현승고。문랍법신간예능조알CUMS유도적상술변화;문랍법신처리대정상대조대서적행위、SOD、MDA화5-HTT급NET표체무명현영향。결논문랍법신억제CUS유도대서출현초필억욱양행위적궤제지소부분여기개선뇌내양화응격평형,역전5-HTT화NET이상표체유관。
Aim To investigate if anti-depressive effect of venlafaxine was associated with improving oxi-dative stress and expression of hippocampus NET and 5-HTT in rat model induced by CUS. MethodsEighty SD male rats were randomly divided into four groups:model group(MG),normal group(NG), ven-lafaxine-treated normal group ( VNG ) , and venlafax-ine-treated model group ( VMG) . VNG and VMG were given venlafaxine (23. 4 mg·kg-1 ·d-1 ) once daily;NG and MG were given the same volume solvent. Soli-tary condition with chronic unpredicted stress ( CUS ) was taken to establish rat depression model. The force swimming test was used to evaluate the behavior chan-ges of experimental rats. The malondialdehyde ( MDA) level and activity of superoxide dismutase ( SOD ) in serum were determined by biochemical methods. The mRNA and protein expressions of NET and 5-HTT in <br> hippocampus were determined by Real-Time Reverse transcription polymerase chain reaction ( real-time RT-PCR) and Western blot ( WB) , respectively. Results Compared with NG rats, obviously increasing immo-bile time of rats in force swimming test and serum MDA level, as well as significantly decreasing SOD activity in serum was observed with clearly decreasing 5-HTT expression and elevating NET expression in hippocam-pus of MG rats. The treatment of venlafaxine distinctly suppressed changes above from CUS-induced rats. However, significant changes failed to be found in VNG rats. Conclusion The anti-depressive effect of venlafaxine may at least partly involve in improving ox-idative stress/anti-oxidative stress balance and revers-ing abnormal expression of NET and 5-HTT.