中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2014年
4期
484-490
,共7页
程瑞凤%景晶%华冰%薛旻秋%陆钊罡%赵伟鸿%樊紫周%果嘉%杨卫东%王英华%彭晓东
程瑞鳳%景晶%華冰%薛旻鞦%陸釗罡%趙偉鴻%樊紫週%果嘉%楊衛東%王英華%彭曉東
정서봉%경정%화빙%설민추%륙쇠강%조위홍%번자주%과가%양위동%왕영화%팽효동
抑郁症%甘草%黄酮%5-羟色氨酸%单胺氧化酶%5-羟色胺能神经元
抑鬱癥%甘草%黃酮%5-羥色氨痠%單胺氧化酶%5-羥色胺能神經元
억욱증%감초%황동%5-간색안산%단알양화매%5-간색알능신경원
depression%Glycyrrhiza uralensis Fisch.%fIavonoids%5-hydroxy-L-tryptophan%monoamine oxidase%serotonergic neurons
目的：探讨甘草总黄酮提取部位（LF）的抗抑郁作用及可能的作用机制。方法 Km 小鼠分别每天 po给予 LF 5，30和180 mg·kg-1，连续21 d，于第1天、第7天和第21天给药后1 h进行强迫游泳实验（FST），记录4 min 内不动时间；另取 Km 小鼠，按照 FST 的实验分组处理，于第1天、第7天和第21天 po药后1 h 进行悬尾实验（ TST），记录4 min 内不动时间。ICR 小鼠分别每天 po给予 LF 50，150和400 mg·kg-1，连续7 d，进行利血平诱发症状拮抗实验（ART），于末次给药后1 h采用记录小鼠运动不能、上睑下垂和监测肛温；另取 Km 小鼠，分别每天 po给予 LF 50，150和400 mg·kg-1，连续7 d，于末次给药1 h后 sc 阈致死剂量的育亨宾，观察24 h 小鼠存活情况；取 Km 小鼠，分别每天 po给予 LF 50，150和400 mg·kg-1，连续7 d，第8天进行5-羟色氨酸诱导的甩头实验（HTT），记录30 min 内的甩头次数，并检测皮质、海马和丘脑中单胺氧化酶（mAO）活性。结果 FST 和 TST 实验结果显示，与正常对照组比较，LF 能够减少小鼠游泳和悬尾的不动时间（P﹤0.05），且与氟西汀有相似的时-效特点。ART 实验结果显示，LF 能够拮抗给予利血平1 h 后引起的小鼠上睑下垂和运动不能（P﹤0.05），但不能够拮抗4 h 后引起的小鼠体温降低。LF 对育亨宾阈致死剂量引起的小鼠死亡没有协同增加作用；LF 150和400 mg·kg-1均能明显协同增加注射5-羟色氨酸后甩头次数（P﹤0.05），小鼠皮质、海马和丘脑中 mAO 活性与正常对照无差异。结论 LF在急性绝望小鼠模型上具有抗抑郁样作用，其作用机制可能与其直接增强脑内5-羟色胺能神经功能有关。
目的：探討甘草總黃酮提取部位（LF）的抗抑鬱作用及可能的作用機製。方法 Km 小鼠分彆每天 po給予 LF 5，30和180 mg·kg-1，連續21 d，于第1天、第7天和第21天給藥後1 h進行彊迫遊泳實驗（FST），記錄4 min 內不動時間；另取 Km 小鼠，按照 FST 的實驗分組處理，于第1天、第7天和第21天 po藥後1 h 進行懸尾實驗（ TST），記錄4 min 內不動時間。ICR 小鼠分彆每天 po給予 LF 50，150和400 mg·kg-1，連續7 d，進行利血平誘髮癥狀拮抗實驗（ART），于末次給藥後1 h採用記錄小鼠運動不能、上瞼下垂和鑑測肛溫；另取 Km 小鼠，分彆每天 po給予 LF 50，150和400 mg·kg-1，連續7 d，于末次給藥1 h後 sc 閾緻死劑量的育亨賓，觀察24 h 小鼠存活情況；取 Km 小鼠，分彆每天 po給予 LF 50，150和400 mg·kg-1，連續7 d，第8天進行5-羥色氨痠誘導的甩頭實驗（HTT），記錄30 min 內的甩頭次數，併檢測皮質、海馬和丘腦中單胺氧化酶（mAO）活性。結果 FST 和 TST 實驗結果顯示，與正常對照組比較，LF 能夠減少小鼠遊泳和懸尾的不動時間（P﹤0.05），且與氟西汀有相似的時-效特點。ART 實驗結果顯示，LF 能夠拮抗給予利血平1 h 後引起的小鼠上瞼下垂和運動不能（P﹤0.05），但不能夠拮抗4 h 後引起的小鼠體溫降低。LF 對育亨賓閾緻死劑量引起的小鼠死亡沒有協同增加作用；LF 150和400 mg·kg-1均能明顯協同增加註射5-羥色氨痠後甩頭次數（P﹤0.05），小鼠皮質、海馬和丘腦中 mAO 活性與正常對照無差異。結論 LF在急性絕望小鼠模型上具有抗抑鬱樣作用，其作用機製可能與其直接增彊腦內5-羥色胺能神經功能有關。
목적：탐토감초총황동제취부위（LF）적항억욱작용급가능적작용궤제。방법 Km 소서분별매천 po급여 LF 5，30화180 mg·kg-1，련속21 d，우제1천、제7천화제21천급약후1 h진행강박유영실험（FST），기록4 min 내불동시간；령취 Km 소서，안조 FST 적실험분조처리，우제1천、제7천화제21천 po약후1 h 진행현미실험（ TST），기록4 min 내불동시간。ICR 소서분별매천 po급여 LF 50，150화400 mg·kg-1，련속7 d，진행리혈평유발증상길항실험（ART），우말차급약후1 h채용기록소서운동불능、상검하수화감측항온；령취 Km 소서，분별매천 po급여 LF 50，150화400 mg·kg-1，련속7 d，우말차급약1 h후 sc 역치사제량적육형빈，관찰24 h 소서존활정황；취 Km 소서，분별매천 po급여 LF 50，150화400 mg·kg-1，련속7 d，제8천진행5-간색안산유도적솔두실험（HTT），기록30 min 내적솔두차수，병검측피질、해마화구뇌중단알양화매（mAO）활성。결과 FST 화 TST 실험결과현시，여정상대조조비교，LF 능구감소소서유영화현미적불동시간（P﹤0.05），차여불서정유상사적시-효특점。ART 실험결과현시，LF 능구길항급여리혈평1 h 후인기적소서상검하수화운동불능（P﹤0.05），단불능구길항4 h 후인기적소서체온강저。LF 대육형빈역치사제량인기적소서사망몰유협동증가작용；LF 150화400 mg·kg-1균능명현협동증가주사5-간색안산후솔두차수（P﹤0.05），소서피질、해마화구뇌중 mAO 활성여정상대조무차이。결론 LF재급성절망소서모형상구유항억욱양작용，기작용궤제가능여기직접증강뇌내5-간색알능신경공능유관。
OBJECTlVE To investigate the antidepressant effect and reIated mechanism of the totaI fIavonoids extract parts( Iicorice fIavonoids,LF)from Glycyrrhiza uralensisFisch. cuItivated IocaIIy in Ningxia. METHODS Forced swimming test( FST)and taiI suspension test( TST)were adopted to study the antidepressant pharmacoIogicaI effect in the acute stress-induced depression modeI in mice. The Km mice were intragastricaIIy administered with LF(5,30 and 180 mg·kg-1 )once daiIy,for 21 con-secutive days. One hour after the first,seventh and Iast administrations,the mice were submitted to FST by recording the immobiIity period within the Iast 4 min of the totaI 6 min in both tests and the resuIts were expressed as decrease in immobiIity period with respect to vehicIe controI. In TST,the other group of Km mice was used to evaIuate the antidepressant effect in same protocoI. In the antagonism of reserpine-induced symptoms test( ART),ICR mice were administered intragastricaIIy with LF( 50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days. One hour after the Iast administration,the mice received reserpine(4 mg·kg-1 ,ip),and ptosis or akinesia was measured 1 h after reserpine injection whiIe rectaI temperature was measured 4 h after the reserpine injection respectiveIy. The same protocoI was adopted in yohimbine toxicity potentiation test(YTT)as in ART. Thirty minutes fter the Iast adminis-tration,the mice received the threshoId IethaI dosage of yohimbine(30 mg·kg-1 ,sc)respectiveIy,and the death number of the mice was caIcuIated in 24 h after the yohimbine administration. In the 5-hydroxy-L-tryptophan(5-HTP)induced head-twitches test(HTT)in mice,after being administered intragastricaIIy with LF(50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days,the mice received pargiIine (100 mg·kg-1 ,ip)the next day,and 30 min Iater,5-HTP(10 mg·kg-1 ,ip)was intraperitoneaIIy injec-ted to induced the head twitch respectiveIy,and the times of head twitch in a 30 min period after 5-HTP treatment were observed at 6 time points. After HTT,the mice were sacrificed quickIy,and the mono-amine oxidase(mAO)activity in the brain cortex,hippocampus and thaIamus was examined to evaIuate the antidepressant effect of fIavonoids with mAO inhibition. RESULTS Compared with the vehicIe controI,LF significantIy decreased the immobiIity period in both FST and TST(P﹤0.05). LF(50,150 and 400 mg·kg-1 )antagonized the ptosis and akinesia symptoms respectiveIy in 1 h after reserpine administration( P ﹤ 0. 05 ), but faiIed to antagonize hypothermia produced 4 h after reserpine administration. AIso,at the same dosage,LF did not synergeticaIIy produce the enhancement of death by subcutaneous injection of yohimbine at the threshoId IethaI dosage. LF(150 and 400 mg·kg-1 )couId significantIy and synergeticaIIy increase 5-HTP induced head-twitches response(P﹤0.05),but LF couId not promote mAO activity in the cortex,hippocampus and thaIamus at the same dosage. CONCLUSlON LF exerts antidepressant-Iike effect on the modeI of acute despair test. The mechanism might be reIated to direct enhancement of the serotonergic neuraI function in the brain.
