TAC DONG CUA BERBERIN VA PALMATIN TREN TRI NHO HINH ANH VA KHONG GIAN CUA CHUOT NHAT
Nguyen Hodi Nam', Vo Phiing Nguym*, Trdn HUng*
TOM TAT
Muc tieu: Trong nghien deu nay, hieu qud cua berberin va palmatin tren khd ndng hgc hdi thu nhqn vd ggi nhdc tri nha hinh dnh vd kliong gian dugc klido sdt tren chugt nlidt gdy mat tri nha bdi scopolamine trong md hinh thie nghiem nhan dien hinli dnh (objed recognition) va klidng gian (Morris Water Maze).
Phwmg phdp: Trong qud trinh thu nhqn tri nhd, chugt bi iec dit thu nlidn tri nhd Mnh dnh vd klwng gian bdi scopolamine Img/kg tiem dudi da. Trong qud trinli ggi nhac tri nhd, chugt bj gdy mai tii nitd Ididng gtan da hinh thdnh bai scopolamin 3 mg/kg tiem du&i da vd gdy ra mai tri nhd hinh dnh bdi scopolamine Img/kg tiem phuc md. Lieu dUng ciia Berbeiin vd Palmatin klido sdt trong cd 2 qud trinh Id 50 mg/kg vd 100 mg/kg.
Ket qud: Berberin vd Palmatin dugc cho udhg lieu 50 mg/kg vd 100 mg/kg cai thien tinh trang mdi tri nhd gdy ra bai scopolamine b chugt trong cd 2 qud trinh hgc hdi thu nltdn tri nhd vd gai nhdc tri nhd klii so sdnh v&i nhdm chimg.
Ket ludn: Cdc kei qud tit mo liinh Morris Water Maze vd Objed Recognition (acd2 qud tiinh) dung chudt dd ldm suy gidm tri nh& bdng scopolamin, chung tdi thmf rdng berbenn vd palmatin dd cdi thien khd ndng hgc hdi vd tri nha khong gian va hinh dnh dia chudt. Tdc dgng ndy kltdc khdng cd y nghia vdi tdc ^ng ciia galantamin, mgt dmi uc die acetylcholinesterase, diegc sie dung trong diiu tri berth Alzhdmer.
Tit khoa: Alzhdmei; Ba-herin, Palmatin, Scopolamin, Acetylcholinestei-ase, Da hinh nie&c Monis Water Maze, Nhan dien vqt the.
ABSTRACT
EFFECTS OF BERBERIN AND PALMATIN ON MOUSE'S OBJECT RECOGNFTION AND SPATIAL MEMORY
Nguyen Hoai Nam, Vo Phung Nguyen, Tran Himg
* Y Hoc TP. Ho Chi Minh * Vol. 14 - Supplement of No 1 - 2010: 64-72 Objectives: In this study, the efficacy of berberin and palmatin on leaming to acquire memory and memory retrieval was evaluated on scopolamine-induced amnesia mice in the Object recognition and Morris Water Maze test.
Methods: Mice with amnesia in acqidred process were induced by scopolamine 1 mg/kg, SC. In retiieval process, mice were caused memory to loss tlmt was established before by scopolamine 3 mg/kg, IP (spatial memory) or scopolamine 1 mg/kg, SC (object recognition memoiy). In this study, doses of berbenn and palmatin to evaluate in both 2 processes were 50 mg/kg and 100 mg/kg.
Results: The berberin or palmatin given orally at the doses of 50 mg/kg and 100 mg/kg B.W. abolished the amnesic effed of scopolamine in objed regconition test and water maze test in 2 processes such as acquire and retrieval memory when compared with control group.
Conclusions: In conclusion, based on the results ofthe Morris wata- maze tests and Object recognition test (in both two processes) using mice with amnesia induced by scopolamine, we found that berbain and palmatin
' Khoa Duac • Dai hpc Y Dircrc Tp. Ho Chf Minh
Dia chl lien ftp DS. Nguyen Hoai Nam DT 0937 859 209 Email hoainiim d2U(14(g'vithoo c.
had improved leaming and memory capacit)/ tlmt impaired by scopolamine. Tlie adivities of berbenn ai palmatin on scopokmhiE -induced amnesia mice are not significantly different with galantamin}''^
accti/ldtolinesterase inhibitor, has been used in tlte ti-eatment of Alzheimer's Disease.
Keyzvords: Alzhdmer, Berberin, Palmatin, Scopolamin, Acetylcholinesterase, Morris Water Maze, Object recognition.
M O DAU
Berberin va Palmatin la cae alkaloid duge chie't xuat tir dupc lieu, each diing ciing nhu tic dpng dugc Iy cua chiing da dupc nghien Cliu kha nhieu va dat biet la tien tae dgng khang cholinesterase in-vitio(ll),(6),(10) va tac dpng phye hoi tri nhd bi suy giam bdi scopolamin tien tii nhd khdng gian in-vivo (4), cd tiem nang tiong dieu tri cac benh lien quan tdi suy giam tri nhd.
MVC TIEU
Trong pham vi de tai nay, chiing tdi tien hanh nghien eiiu tac dgng ciia berberm va palmatin tren chiie nang van dpng tu nhien, anh hudng tien sy phbi hgp van ddng, tri nhd hinh anh va tii nhd khdng gian d ca hai qua tiinh hpc hdi thu nhan tri nhd va qua trinh goi nhae tii nhd da hinh thanh bi lam suy giam bdi scopolamin.
D O I T U O N G - m U d N G PHAPNGHENCUtl Chudt nhat tiang chiing Swiss albino, khde manh, do Vi?n vacxin va sinh pham y te Nha Trang cung cap. Chugt duge nudi on dinh thanh nhdm 6-8 chudt tiong mpt hop nhua tiing kieh thudc 28 x 30 x 15 {rgng x dai x eao) (em), mpt tijan tiudc khi thu nghiem trong mdi tiudng ehu trinh 12 gid sang tdi (7 gid -1 9 gid) cd nhi?t dp phdng la 27 C , vdi thiic an cam vien thanh phan bpt gao, bdt bap, vitamin bd sung do Vi?n vacxin va sinh pham thanh phb Nha Trang cung cap.
Thuoc thii nghiem
Scopolamin HBr (Sigma) do cdng ty Sigma cung cap.
Diazepam (Valium^) 5mg, do edng ty Roche san xuat.
Galantamin (Reminyl f) 4 mg, do cdn Janssen -cilag san xuat. D cong ty
Berberin va Palmatin do bd mdn Dirge li^- Khoa Dugc - Dai hpc Y Dupc TpHCM chiS xuat, phan lap va tinh che.
Phuong phap nghien cmi
Khao sdt tdc dgng tren chiic ndng van dgng tu nhien-Mo hinh moi truatig ma (Open Field) (1)
Chupt dupe ehia ngau nhien thanh 5 Id m6i Id 6 - 8 con
Ld chiing : uong nudc cat, 0,1 ml/lOg the tipng.
Lo chat thii: ud'ng Berberin chlorid duge pha tiong nudc cat vdi eae h^u 50 mg/kg va IOO mg/kg.
Ld chat thii: uong Palmatin sulfat dupc pha tiong nude cat vdi eac Heu 50 mg/kg va 100 mg/kg.
Sau khi udng thudc chupt duoc dat nh?
nhang vao mdt gdc ciia hop nh^ra vdi cirdng dp anh sang la 100 ± 5 lux va cho phep chupt di chuyeh tu do trong hop nhua tiong vdng 30 phiit. Ho^t dpng ciia chugt tiong hop nhya dupc ghi hinh va xem lai. Dem so d chupt di chuyen va so Fan chupt diing tren hai ehan sau tiong timg khoang 5 phiit. Chupt dupc xem la di chuyen vao tiong mpt d khi dat ca 4 chan vao 6 do. Thubc dupc xem la cd anh hudng den chiic nang van ddng tu nhien eua chugt khi lam tiiay dbi khoang dudng di chuyeh ciia chudt (so d) va sb Ian diing tien hai chan sau ciia chupt so vdi 16 chiing.
Khdo sdt tdc dong tren suphoi hap van dgng -Mo hinh thanh quay (Rotarod) {2),(J)
Thiet bi Joints & Roberts (Rota - Rod Aeceler For Mice 7650) dupc sii dung tiong thii nghiem nay.
Chudt dupe hua'n luyen tiong vdng hai ngay trude khi tien hanh thii nghiem. Co dinh sb vdng quay la 30 vdng/phiit. Cho chugt Ian luot len thanh quay tidn, quan sat tiong 5 phut, nhiing chupt roi khdi thanh quay trong vdng 5 phiit bi loai ra khdi tiiii nghiem.
Thii nghiem duge tie'n hanh sau 30 phut dimg chat thu hay chat ddi ehieu. Chudt dugc ehia ngau nhien thanh 6 Id moi Id 6-8 chupt.
Ld chiing: cho ehupt ubng nudc cat vdi lupng 0,lml/10g the tiong
Ld thii; cho ubng Berberin chlorid pha tiong nude eat vdi lieu 50 mg/kg va 100 mg/kg, 0,lml/10g tipng lupng.
Lo thii: eho uong Palmatin sulfat pha tiong nudc cat vdi lieu 50 mg/kg va 100 mg/kg, 0,lml/10g tipng lupng.
Ld dbi ehieu: cho ubng diazepam (Vahum^) dugc pha tiong nude cat h'eu 10 mg/kg.
Ghi nhan thdi gian chudt roi khdi thanh quay ciia mdi Id, neu sau 5 phiit chupt khdng roi khdi thanh quay ghi nh|n thdi gian la 3(X) giay.
Thubc dugc xem la cd tae dgng khi lam giam tiem thdi roi khdi tiianh quay ciia chupt.
Khdo sdt tri nha nhdn dien hinh dnh - Object Recognition (5)
Chudt duge chia ngau nhien thanh 7 Id: mdi Id tit 6 - 8 chupt
Pha hgc hoi, thu nhqn tri nha
Ld chiing: tiem dudi da dung dich NaCl 0,9%; 0,1 ml/lOg tipng lupng, 30 phiit tiudc khi bat dau Tl (Chiing).
Lo mat tri nhd: tiem dudi da scopolamin hydrobromide dupc pha tiong dung dieh NaQ 0,9%, lieu 1 mg/kg, 0,1 ml/lOg tipng lupng, 30 phiit trudc khi bat dau Tl (Scop).
Ld dbi chieu tiem dudi da scopolamin hydrobromide dugc pha tiong dimg dich NaQ 0,9%, Ueu 1 mg/kg, 0,1 ml/lOg chugt, ngay sau dd cho ubng galantamin (Reminyl^^) dupc pha trong nude cat h'eu 2,5 mg/kg, 0,1 ml/lOg trpng Iugng, 30 phiit trude khi bat dau Tl (Scop + Gal
2,5).
Dbi vdi cae Id chat thii Berberin va Palmatine, 30 phiit trudc khi bSt dau Tl, scopolamin h)'drobromide dugc pha tiong dung dich NaQ 0,9% tiem dudi da, heu 1 mg/kg, 0,1 ml/lOg chupt va ngay sau dd cho uong hoac Berberin chlorid hoac Palmatin sulfate dupe pha tiong nudc cat d cac lieu 50 mg/kg, 100 mg/kg vdi the ti'eh eho ubng la 0,1 ml/lOg tigng lupng (Scop + Ber 50; Scop + Ber 100; Scop + Pal 50;
Scop + Pal 100).
Pha ggi nhdc tri nha
Trong pha nay chudt cung dugc tiem scopolamin va cho udng chat thii nghiem nhu tren, nhung thdi diem thuc hien tiem va cho ubng la ngay sau khi da dupc hpc hdi tiong thii nghiem Tl
Mdt ngay trudc thii nghiem, mdi ehupt duge cho vao mdt hdp nhira thii nghiem rieng (khdng CO vat khao sat) de kham pha thiet bi tiong vdng 10 phiit, eac hop nhua nay dugc dat d vi tri se tieh hanh thu nghiem.
Thii nghiem huah luyen Tl: Lan lupt timg hpp nhua thii dugc dua vao diing \'i tri thii nghiem, cd camera ghi hinh. Hai vat khao sat hoan toan giong nhau dugc d|t vao hop nhua mpt each can xiing, dbi dien nhau, each canh ngan va eanh dai oia hop nhua lan lugt 6 cm va 8 cm. Chudt dugc dat nhe nhang vao giiia hop nhua va duge kham pha 2 \'at the gibng nhau nay tiong 10 phiit. Sau thii nghiem Tl chudt dupc dat tid lai vao chuong nudi sau khoang thdi gian 3 gid bat dau thu nghiem T2.
Thu nghiem lua chpn T2 (choice tiiai):
trong subt thir nghiem T2 mdt vat la (novel) dupe thay cho mdt tiong hai v$t quen (familiar) da hien dien trong thir nghiem huah luyen Tl;
ciing cho chudt kham pha hai vat khac nhau nay tiong 10 phiit.
Vat the khao sat vat the dimg cho ehupt nhan bie't dupc lam bang inox mau tiang, cd hinh khdi lap phuong ( 1 x 1 cm) hay hinh tru {<I>
lem), vdi ehieu eao 1,5 cm. Cac vat the nav
khdng mill, khdng qua quan trong hay ah tiiong vdi chugt. Cudng do anh s ^ g dimg tiong thu nghiem la 100 ±5 lux.
Tl sb kham pha vat quen va 1? E (Exploration ratio) dupc coi nhu ehi sb chmh de do kha nang ghi nho tiong thii nghiem nay, dupc tinh nhu sau: E=N/F
Thubc dugc xem la cd tac dgng khi lam tang ti sb kham pha vat quen va la.
Khdo sdt tri nhanhdn dim khonggian-Mo hinh do htnh nuac (Morris Water Maze) (3),(6) ,(9),(n)
Be chiia nudc hinh tidn bang inox, dudng kinh 1,5 m, chieu cao 80 cm, dugc dan decal den d mat tiong, bbn diem dupc phan bo bang nhau dpc theo chu vi ciia be dugc diing nhu nhung vj tri khdi dau. Be' duoc chia thanh bbn phan bang nhau va mdt chan de nhd (cao 25 cm) duge dat vao chinh giiia ciia mpt tiong nhung phan tu nay. Vi tri dat ciia ehan de dugc cd dinh tiong subt thdi gian thir nghiem.
Xung quanh be nude dupc bb tri 3 hinh anh d 3 vi tii khac nhau dugc sir dung nhu nhiing dinh hudng khdng gian. Muc nudc tiong be cao hon chan de 0,5 cm, nhiet do 27 "C ± 1 Klido sdt tdc dgng len pha hoc hdi, thu nitqn tri nhd
Chupt dupe ehia ngau nhien thanh 5 Id:
mdi Id tir 6 - 8 chugt
Ld chimg: dung dich NaCl 0,9%, SC, 0,1 ml/lOg the tigng, 30 phiit trudc khi bat dau Tl.
Ld mat tri nhd: tiem dirdi da scopolamin h\'drobroniide dupe pha tiong dung dich NaQ 0,9%, h'eu 1 mg/kg, 0,1 ml/lO g tipng lupng, 30 phiit trudc khi bat dau Tl (Scop).
Ld ddi chieu tiem dudi da scopolamin hydrobromide dugc pha tiong dung dich N a a 0,9%, h'eu 1 mg/kg, 0,1 ml/lOg chugt, ngay sau dd cho uong galantamin (Reminyl®) dupc pha tiong nude cat Heu 5 mg/kg, 0,1 ml/10 g tipng lupng, 30 phiit trudc khi bat dau Tl (Scop + Gal 5 mg/kg).
E)di vdi cac Id chat thu Berberin vj Palmatine, 30 phut trudc khi bit dau Tl, scopolamin h)'drobromide dupc pha tiong dung dich N a Q 0,9% tiem dudi da, lieu i mg/kg, 0,1 mlAO g chugt va ngay sau do dw udng hoac Berberin Chlorid hoac Palmatin sulfate duge pha tiong nude cat d cae lieu 50 mg/kg va 100 mg/kg, vdi the tich cho udng ia 0,1 ml/10 g tipng lugng (Scop + Ber 50; Scop+
Pal 50, Scop + Ber 100; Scop + Pal 100).
Chupt dupc huah luyen va thu nghidm trong vdng 7 ngay.
Ngay dau tien (0) chugt dugc cho boi ti; do trong vdng 60 giay de lam quen vdi ho.
Ngay 1-5: tien hanh vdi 2 thir nghiem, moi thir nghiem each nhau 20 phiit. Trong 1 thir nghiem, chudt dugc cho bai trong 120 giay de tim chan de an dudi mat nuoe. Sau khi ket thuc tiiii nghiem Tl chupt dugc lau kho, dat vao keo tiiiiy tinh va dupe sudi ain bang den chieu tia hong ngoai trong 15 phiit de bat dau cho thti nghiem T2, ket thiic thir nghiem T2 chugt ciing dugc sudi ani nhu tien sau do tia ve ehuong nudi. Trong subt qua trinh huMi luyen neu ket Ihiie 120 giay ma chupt khong tim thay chan de thi hudng dan chugt tim den chan de bSng each dat ngdn tay len tren chan de va eho phep chupt diing dd trong 10 giay de quan sat xung quanh trudc khi dd chupt ra khdi be nudc.
Ngay thii 6: tien hanh thir nghiem vdi chan de dupc lay ra khdi ho nudc. Chupt dupe cho boi tiong hb vdi thdi gian 60 giay. Ket thiic thir nghiem, lay ehupt ra khdi ho va lau khd.
Khdo sdt tdc dgng tren pha gai nhac tri nho sau khi tri nhd dd hinh thdnh.
Chudt dupc chia ngau nhien thanh 4 16:
mdi Id tir 6 - 8 chupt. Chugt trong eac Id duoe huah luyen tiong 4 ngay, mdi ngay 2 thii nghiem tuong tu trong huah luyen tiong pha hge hdi, thu nhan tri nho. Tuy nhien scopolamin va cae chat thir chi dupe sir diuig vao ngay danh gia (ngay thii 5).
Danh gia tac ddng cua thuoe qua viec so sanh tiem thdi tim den chan de cua chudt, thdi gian chudt trai tiai qua tix)ng Vi hb cd chii chan de va so Ian chudt boi qua vi tri dat chan de giiia cac Id vdi nhau.
Thong ke kei qud
Dit lieu dupe trinh bay d dang sb tiung binh (TB) ± sai sb chuan a i a sb trung binh (SEM). So lieu dupc thbng ke bSng phan mem
Minitab 14.0. Cae dav sb lieu dupe so sanh bing phep kiem Kruskal Wallis, neu ed su khae nhau se tie'p tuc dupc so sanh timg cap bang phep kiem Mann Whitney. Do thi dupc ve bang phan mem SigmaPlot 10.0.
KET QUA NGHIEN C L / U
Anh huang oia berberin va palmatin tren chiic nang v ^ dong tu nhien
Hinli 1. (A) Klioang du&ng di chuyeh ciia chugt (sod); (B) 5,10,15, 20,25,30 phut sau klii dung thuoc Berbmn (501 100 mg/kg, udhg) trong md hinh mdi trudng md
Tai cae thdi diem 5, 10, 15, 20, 25 va 30 phiit sau khi uong Berberin, cac Id dimg Berberin va Palmatin lieu 50 mg/kg va 100 mg/kg, cho ubng cd lam gia tang khoang dudng di chuyen va so Ian diing tien 2 ehan sau eua chupt nhung su khac biet giiia cac Id nay so vdi Id chiing van chua cd y nghia thbng ke vdi khoang tin cay 99%. Khoang dudng di chuyen va sb lan diing tren 2 ehan sau ciia chupt Cling tang khi tang lieu, tuy nhien su thay dbi nay chua ed y nghia thbng ke so vdi Id ehiing va Id dimg lieu thap hon. Chiic nang van dpng tu nhien eua chudt ud'ng Berberin va Palmatin d cac Heu khao sat cung khdng khac cd y nghia khi so sanh vdi nhau tiong suot 30 phiit sau khi dupe cho ubng.
Nhu vay, Berberin va Palmatin d lieu khao sat khdng anh hudng den chuc nang van ddng tu nhien va hoat ddng kham pha ciia chudt tai cac thdi diem sau khi ubng.
ldn dung ti-en 2 didn sau dta diugt tqi cdc thdi diein mg/kg vd 100 mg/kg, ud'ng), Palmatin (50 mg/kg vd
Anh huofng cua berberin va palmatin tren chiic nang phoi hgp van dong
Hinh 2. Tiem thai rai khdi thanh quay dm chudt trong 30 plidt vd 60 plidt sau klii uo'ng Berberin (50 mg/kg, 100 mg/kg), Palmatin (50 mg/kg, Palmatin 100 mg/kg) vd diazepam 10 mg/kg trong mo hmh thanli quay. ***P<0,001 so v&i nlidm chimg vd cdc nhdm uong Ba-berin vd Palmatin (50 mg/kg 100 mg/kg).
Tai thdi diem 30 va 60 phut sau khi sir dung thubc. Id uong Berberin (50 mg/kg va 100 mg/kg) va Id uong Palmatin (50 mg/kg va 100 mg/kg) khdng Iam thay ddi tiem thdi chudt roi khdi thanh quay cd y nghia thong ke khi so vdi Id chiing vdi khoang tin cay 99%
Cdn Id uong diazepam 10 mg/kg lam giam tiem tiidi chupt rai khoi tiianh quay ed y nghia thbng ke (PO.OOl) khi so vdi Id ehiing. Id ud'ng Berberin (50 mg/kg, 100 mg/kg) va Id ubng Palmatin (50 mg/kg, 100 mg/kg).
Xhu vay, Berberin \ a Palmatin khdng anh hudng len chiic nang phbi hgp van ddng ciia ehupt d h'eu khao sat. Cac tiiir nghiem lien quan den tri nhd cd sir anh hudng bdi chiie nang phbi hop van ddng se khdng hi anh hirdng o cae h'eu khao sat 50 mg/kg va 100 mg/kg.
Tac dpng cua berberin va palmatin tren tri nho hinh anh
* Pha hpe hoi, thu nhan tri nhd
Hinh 3. Anli hirang tren ti sokhdm plid vqt klido sdt quen vd la trong md hinh tri nha hinh dnh dia cdc didi thir nghiem, '*P<0,01 so vdi Id scopolatnin,
"P<O,01 so v&i Id diimg.
- Ld tiem dudi da scopolamin 1 mg/kg lam giam ti sb kham pha vat khao sat quen va la ed y nghia thbng ke (*# P<0,01) so vdi Id chiing.
- Cac Id eho ubng Berberin (50 mg/kg va 100 mg/kg). Id cho ubng Palmatin (50 mg/kg, 100 mg/kg) va Id eho ubng Galantamin 2,5 mg/kg ngay sau khi tiem dudi da scopolamin 1 mg/kg cd tac dpng lam tang ed y nghia thbng ke (**P<0,01) ti so kham pha vat khao sat quen va la khi so sanh vdi Id chi tiem dudi da scopolamin 1 mg/kg.
- Sv khae bi^t ve ti sb kham pha giiia eac Id chiing. Id tiem scopolamin 1 mg/kg + Berberin (50 mg/kg, 100 mg/kg, ubng), Id tiem scopolamin 1 mg/kg + Palmatin (50 mg/kg, 100
jng/kg, ubng) va Id tiem scopolanun 1 mgflijil Galantamin 2,5 mg/kg m?c dii cd thay sy khi biet nhung su khac biet nay khbng cd y n ^ thbng ke (khoang tin cay 99%).
Nhu vay: Scopolamin 1 mg/kg, tiem dirfi da cd tac ddng pha huy su thu nhan tri nhg trong qua tiinh huah lu)'en thir nghiem T]
Berberin (50 mg/kg va 100 mg/kg), Palmalii (50 mg/kg va 100 mg/kg) va Galantamin 2,:
mg/kg cd tae ddng bao ve va ngan ch^n svpM hiiy tien trinh thu nhan tri nhd hinh anh gayn bai viec tiem dudi da scopolamin 1 mg/kg. Sy khac biet d cac Id dieu tri chua cd y n^"a thbng ke, khoang tin eay 99%.
* Pha goi nh^e tri nhd hinh anh da hinh thanh.
Hinh 4. Anh hu&ng cim cdc chM thie nghiem tren ti so'kltdm phd vqt klido sat quen vd Iq trong mo hinh tri nli& liinh dnh, **P<0,01 so v&i Id scopolamin, ttP<0,(&
so vai 13 diieng.
Ld scopolamin tiem dudi da vdi lieu 1 mg/kg lam giam ti sb kham pha vat quen va k cd y nghia thong ke (^P<0,05) d khoang tin cay 99% khi so sanh vdi Id ehiing
Cac Id cho ubng Berberin (50 mg/kg va 100 mg/kg) va Palmatin (50 mg/kg va 100 mg/kg) ro tac dpng lam tang ti so kham pha vat quen vai*
cd y nghia tiibng ke (**P<0,01) khi so sanh vdi 16 chi tiem scopolamin 1 mg/kg, tiem dudi da, khoang tin cay 99%.
Nhu vay, scopolamin d Heu 1 mg/kg tiem dudi da cd tac dpng pha huy qua trinh gpi nhac tri nhd hinh anh da hinh tiianh trudc dd. Va su pha huy nay bi ngan chan va dao ngugc bdi tac dgng phuc hoi cua berberin (50 mg/kg, ubn^
va palmatin (50 mg/kg, uong) the tren vi?c so sanh ti so kham pha vat quen va la giiia cac lb.
Tac dpng ciia berberin va palmatin tren tri nha khong gian
Pha hoc hoi, thu nhqn tri nha
A B Hinh 5. (A) Tiem thdi ttm deh chdn de trong cdc ngdy hudn luyen; (B) Tiem th&i so sdnh ngdy IvdSa cdc Id
thie, *P<0,05; **P<I,01 so v&i ngdy thii 1 trong citng 1 Id, ''P<0,05; "P<0,01 so sdnh vdi Id scopolamin citng ngdy.
X.
' A * ^ - * ^
^v
A B Hinh 6. (A)Anh huang tren thai gian diudt d trong 1/4 Ho co chiea didn dea ngdy thie 6 ciia cdc chdi thit I niiiem, "P<0,01 so v&i Id diieng, *P<0,05 so v&i 16 scopolamin, **P<0,01 so vdi Id scopolamin. (B) Anh tren so
tan diugt ben qua vi tri dqt didn deo ngdy thie 6 dia cdc dic^ thie nghiem, *P<0,05 so v&i 16 scopolamin, **P<0,01 so v&i 16 sccrpolamin.
O cac Id ehiing, Id tiem dudi da scopolamin 1 mg/kg + ubng Berberin (50 mg/kg va 100 ' mg/kg), Id tiem dudi da scopolamin 1 mg/kg +
! ubng Pahnatin (50 mg/kg va 100 mg/kg) va Id tiem dudi da scopolamin 1 mg/kg + ubng Galantamin 5 mg/kg deu eho thay tae dpng lam tang so Ian chudt boi qua vi tri d|t chan de rd ret so vdi sb Ian boi qua vi tri ehan de eiia chudt Id chi tiem dudi da scopolamin 1 mg/kg, P<0,05 va , P<0,01 d khoang tin cay 99%
Nhu vay, tiong pha hpc hdi, thu nhan tri nhd ve vi tii chan de (thdi gian d Vi ho chii chan de va so Ian boi qua vi tii chan de) thi scopolamin Heu 1 mg/kg tiem dudi da cd tac ddng pha huy tien tcinh thu nhan tri nhd nay. Berberin (50 mg/kg va 100 mg/kg), palmatin (50 mg/kg va 100 mg/kg), hoae galantamin (5 mg/kg) cd tae dgng bao ve, ngan ch|n sir pha hiiy tie'n tiinh nay. Tac ddng cua Berberin va Palmatin d cac h'eu khac nhau ehua eho thay su khae biet cd y nghia va
Cling khdng cd khac biet so vdi Id dimg galantamin.
Pha ggi nhdc tri nhd khong gian dd hinh thanh
Hinh 7. Tiem thai tim deh clidn de trong cdc ngay huan luyen trong thit nghiem ggi nhac tii nhd
Hinh 8. Anh huang dm dmi thie nghiem tren thai gian chugt & trong V* ho cd chiea chan devd sd'lan diuSt ben qua vj tri dqt chdn de, 'P<0,05; "P<0,01 so vai Id chieng, *P<0,05 so v&i Id scopolamin.
Ld tiem phiic md scopolamin 3 mg/kg cd tac dgng lam giam sb Ian boi qua vj tii dat chan de eua chugt, su khac biet cd y nghia thong ke khi so sanh vdi Id chiing (#PO,05).
Ld tiem phiic md scopolamin 3 mg/kg + ubng Berberin 50 mg/kg va Id tiem phiic mo scopolamin 3 mg/kg + uong Pahnatin 50 mg/kg cd tac dpng lam tang thdi gian ehupt d Vi ho ehiia chan de va so Ian chupt boi qua vi tii dat ehan de cd y nghia thbng ke CPO,05; *P<0,01) so vdl 16 scopolamin o khoang tin cay 99%. Su khae bi?t ve thdi gian ehupt boi tiong Vi ho chiia chan de va so Ian boi qua vi tri chan de giiia cac Id (trir 16 scopolamin) tuy cd khac nhau, nhung su khae bi?t nay chua cd y nghia thdng ke, khoang tin cly 99%.
Nhu v^y:
- Scopolamin cd tac dgng lam giam qua trinh hpc hdi thu nhan tin nhd d heu 1 mg/kg, tiem dudi da. 6 heu 3 mg/kg, khi dugc tiem phiic md, scopolamin cd tac ddng tic che qua tiinh gpi
nhae tri nhd khdng gjan da hinh tiianh tren chudt nhat tiang.
- Berberin va Palmatin d lieu 50 mg/kg va 100 mg/kg ed tac dpng phuc hoi lai qua trinh thu nhan tii nhd bi suy giam gay ra boi scopolamin 1 mg/kg, tiem dudi da. Va tac dpng phuc hbi nay khdng khac tac dgng ciia galantamin 5 mg/kg diing dudng ubng khi so sanh ve thdi gian chupt boi trong Vi ho c6 chiia ehan de cung nhu sb lan chupt boi qua vi tri dat chan de.
- Berberm va Palmatin d Heu dimg 50 mg/kg co tac dgng phuc hoi lai qua trinh gpi nhac tri nhd da hinh thanh bi suy giam gay ra b6i scopolamin 3 mg/kg, tiem phiic md.
KETLUAN
Trong thir nghiem khao sat tac dgng cua cua berberin va palmatin tien chiie nang v?n ddng tij nhien va phoi hgp van ddng, cho thav berberin va palmatin d lieu 50 mg/kg khong anh hudng tdi 2 chuc nang nay. Tir dd, tieh hanh thii nghiem khao sat tac dpng ciia
44(2), p p 257-266
berberin va palmatin tren tri nhd khdne eian. Microorganisms and 1 rong mo hinh Morris Water Maze, d ea 2 giai
doan: hpe hdi thu nhan tri nhd va ggi nhie tri nhd da hinh thanh trudc dd cho thay berberin va palmatin d Keu khao sat 50 mg/kg cd tac dgng bao ve va phuc hoi tbt tii nhd khong gian bi lam suy giam bdi seopolamm. Do dd, day cd the la eac thuoc mdi trong nghien ciiu thubc chira benh ve suy giam nhan thiic, dac biet la Alzheimer.
TAI L I | U T H A M K H A O
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