fr liet

Nghien CLFU - Ky thuat

Nghien cu'u tac dung cua tra tan thuy long am doi vol phi dai lanh tinh tuyen tien liet

r r

tren thyc nghiem fr chuot cong trang

Dat van de

Phi dai Idnh tinh tuyin tiin liet Id benh thudng gap d nam gidi tuoi cao. Benh c6 xu hydng tdng len cung vdi tuoi. Benh phi dai Idnh tinh tuyin tien liet d giai doan diu ehu yeu gay rii loan tiiu tien, Idm giam sut chit lugng cudc sing cua benh nhdn. Giai doan sau, niu khdng dugc diiu tri tich eye, khii u phdt triin to, gdy nhieu biin chung rit nang n i (nhiim khuin dudng tiit nieu, sdi tiit nieu, biddi, suy than...) '"* '^.

Hien nay, y hpe hien dai ed rit nhiiu phuang phdp diiu trj ngoai khoa hodn chinh:

elt u tuyin tiin liet qua n6i sol vd phiu thuat triet de m i bde u, hoac cd the diiu trj bao tin blng thuic tdn dugc: nhdm uc ehi a-adrenergic nhu alfuzosin (Xatral), terazosin (Hytrin), doxazosin, nhdm uc chi 5a-reductase nhu finasteride (Proscar) vd dutasteride (Avodart),... Tuy nhien viec diiu trj ngoai khoa khdng phai nai ndo cung cd diiu kien dp dung, mat khde cdc thuic diiu trj n6i khoa tdn dugc cung ed nhiiu tdc dung khdng mong muin vd gid thdnh diiu trj cao '^'''' ^'.

(3 Trung Quic, trong nhlyng nam gin day dd

CO nhiiu cong trinh nghien cuu dieu trj phi dai Idnh tinh tuyin tiin liet blng cdc thuic thao m6c da thu dugc nhung kit qua kha quan '^°'. Y hoc CO truyen Viet nam da cd nhieu bdi thuoc thao mpc dieu tri phi dai Idnh tinh tuyen tiin liet, trong do cd bdi "ty giai phdn thanh im". Tren ca sd' tdc dung cua bdi thuic vd bien chung luan tri cua y hpe CO truyen, chung tdi xdy dung bdi thuic gim

"ty giai phan thanh am" va mpt s i vi thuoc tdng cudng gpi Id bdi "ty giai phdn thanh gia giam".

Tai Vien Y hpe eo truyin Qudn dpi, trong nhung ndm vua qua dd bdo chi trd tan thuy long am, ung dung dieu tri phi dai Idnh tinh tuyin tiin liet vd thiy cd hieu qua nhdt djnh.

16

Tran Lap Cong ', Tran Thanh Tung^

Nguyen Trong Th6ng^ Banh Van Khiru'

' Vien Y hoc Co truyen Qudn doi

^Truang dai hoc Y Hd Noi

De khdng djnh hieu qua diiu tri phi dai Idnh tinh tuyen tien liet cua trd tan thuy long am (TLA), Chung t i i tien hdnh nghien cuu tdc dung cua bdi thuic doi vd'i phi dai Idnh tinh tuyin tiin Net tren thuc nghiem g chupt cing trlng.

Nguyen lieu, ddi tu'O'ng va phu'O'ng phap nghien

CLPU

Nguyen lieu

Tri tan thuy long im g i m cdc dugc lieu vdi

trpng lugng nhu sau:

- Thuy xu'ccng bo {Rhinoma Acori calami) 3,7g - ich chl nhan (Fructus Alpinae oxyphyllaes) 5,0g - Bien xuc {Polygonum aviculare L.) 5,0g - Con b6 (Lamlnaria Japonica areschong) 3,6g - NQLCU tat (Rhizoma Achyranthes bidentata Blume) 5,8g

- Tang phieu tieu {Ootheca mantidls) 2,2g - Ty giai (Rhizoma Dioscorea tokoro Mal^ino) 4,6g - Moc thong (Hocquartia manshuriensis) 3,3g - 0 du'ccc {Radix Lindera myrrha {Lour) Men) 2,7g - VuiDng bM IUTJ hanh (Vaccaria segetalis (Neck.) Garcke) 2,7g

- Lactose 1,0g

Cdc dugc lieu tren dugc niu thdnh cac, sau dd phun sugng va ddng goi dang 5 gam trong tui bac.

Nguyen lieu nghien cu'u:

- Dutasterid (Avodart) vi6n nang 500|ig, cua hang Glaxo Smith Kline;

- Testosteron propionat ong tiem 25mg/1ml cOa hang Tai Yu Chemical & Pharmaceutical Co., Ltd. (Ddi Loan);

- Dau olive, chai 100ml (Italy);

- Ether dugc dung.

D i i tu'ang

Chupt cong trdng due chua truang thdnh,

tuoi tu 40-45 ngdy, cd trpng lygng tu 60-90g do

Hoc vien Quan Y cung cdp. Chupt dugc nu6i

TAP CHi DUQC HQC - 11/2009 (SO 403 NAM 4 ^

Nghien CLFU - Ky thuat

trong d i i u ki$n day du thCfC dn vd nud'c uong tai phdng thi nghiem B6 m6n Dugc ly Trudng dai hoc Y Hd N6i t u 3-5 ngdy trudc nghien CLPU vd trong s u i t thai gian nghien cuu.

Phu'O'ng phap nghien cu'u

Thu nghiem dugc t i i n hdnh theo md hinh gdy phi dai Idnh tinh t u y i n t i i n liet b l n g testosterone theo phuang phdp Dorfronson da dugc cai t i i n '^-^ ^'.

Chupt c i n g t r l n g duge chia n g i u nhien thdnh 5 Id, m i l 16 10 con:

- L6 1 (Chung): tiem d i u olive + uing nude cit2ml/100g/ngdy

- Ld 2 (16 gay m6 hinh): tiem testosteron(TES) + uing nude c i t 2ml/1 OOg/ngay

- L6 3 (16 ehung duang): tiem testosteron + uing dutasterid 40dg/100g/ngdy

- L6 4(thuic nghien cuu): tiem testosteron -t- uing TLA 9g/kg/ngdy

- Ld 5(thuie nghien cuu): tiem testosteron + uing TLA 3g/kg/ngdy

Chu6t 16 1 dugc tiem dung mdi cua testosteron Id d i u olive vdi t h i tich 0,2ml/100g.

Chu6t d cdc 16 2,3,4,5 duge tiem dudi da dui testosteron pha trong d i u olive vdi liiu lOOag/IOOg t h i trpng/ngay (0,2ml/100g), u i n g thuic thu liiu nhu tren lien tuc trong 7 ngdy.

Ngdy thu 8 g i i t chupt b l n g ether, mo bung, bde tach todn bp t u y i n t i i n liet va can b l n g can dien tu. Trpng lugng t u y i n t i i n liet dugc quy theo lOOg t h i trpng chudt, sau dd lam md benh hpe quan sdt vi t h i n h I m theo doi sy b i i n d i i hinh thdi cua t u y i n t i i n liet cdc 16 tai Bp mon Giai p h i u benh - Trydng dai hpe Y Hd Npi.

K§t qua nghien

CLFU

Trong lu'crng t u y i n t i i n liet cua chuot c i n g trdng

Bang 1: Anh hudng cua tri tan thuy long im din trong luang tuyin tiin liet cua chudt cdng tring

L6 nghidn cu'u

L6 1 (chLfng) L6 2(gay m6 hinh)

L6 3 (dutasterid) L6 4 (TLA li6u 9g/kg)

L6 5 (TLA 3g/kg) So vdi 16 1.

n

10 10

10 10

10

Trong l u ^ n g tuy§n tidn Met (mg/100g)

35,95 ± 12,52 83,73 ± 17,86

T 133%' 37,80 ± 6 , 0 7

I 55 %••

63,72 ± 15,19 i 2 4 % "

66,78 ± 18,81 i 2 0 % "

So vai 16 2

P

p 2 - 1 < 0,001

p 3-2 < 0.001 p 4-2 < 0,05 p 4-3 < 0,05 p 5-2 < 0,05 p 5-3 < 0,05 p 5-4 > 0,05

TAP CHi DUQC HQC - 11/2009 (SO 403 NAM 49)

Qua k i t qua bang tr6n cho thay:

(!)• 16 2 trpng lygng tuyen tien li$t sau khi ti6m testosteron tdng rd r6t (133%) so vdi 16 chung vdi p < 0,001. Trong khi dd, d' cdc Id 4, 5 vua tiem testosteron vd u i n g TLA trpng lugng t u y i n t i i n liet d i u giam so vdi Id 2 md hinh gay u xa lanh tinh t u y i n t i i n liet, sy khac biet cd y nghTa thing ke (p < 0,05-0,001), Id dung dutasterid da Idm giam 55 %, hai 16 dung TLA liiu 9g/kg va 3g/kg t h i trpng d i u Idm giam trpng luang tuyin t i i n liet tuang ung la 24 % va 20 %. Tdc dung giam trpng lupng u t u y i n tiin liet cua TLA liiu 9 g/kg vd 3g/kg khde nhau khong ed y nghTa thing ke (p > 0,05).

c i u true vi t h i t i i n liet t u y i n (TLT):

K i t qua k i i m tra hinh thai t u y i n t i i n liet tren kinh hiin vi quang hpe vdi dp phdng dai 100 Ian, cho thiy:

Tuyin tiin liet chupt nh6m chung ed c i u true tuyin va md ke binh thudng (hinh 1) nhung d Id 2 (Md hinh) ed sy thay d i i biiu hien trong Idng mpt s i tuyin ed chua dich tiit mau vang nhat, t i bao tuyin hinh tru hoac vudng, m6t s i tui tuyin Idng rpng, t i bdo biiu m6 t h i p det. Md lien k i t kh6ng tang sinh, kh6ng sung huyit, kh6ng viem.

Tat ca thay d i i do t h i hien hinh thai tuyin v i n trong gidi han binh thudng (hinh 2).

Tuyin tiin liet d 16 3 (dutasterid 40 ^^gl^OO g):

hinh thai cac tuyin cd c i u true binh thudng, Idng tuyin khdng ed dich tiit, s i luang binh thudng, trong Idng mpt s i tuyin chua djch mdu hing hoac cd hing c i u , t i bdo khdng long. Tuy nhien, c6 hinh anh m6 dem cac mach sung huyit t h i hien cua sy sung huyit md lien k i t (hinh 3).

Tyang ty nhu 16 3 hinh anh vi t h i tuyin t i i n liet cua chupt L6 4 (TLA9g/kg) cho thiy: s i lugng tuyin binh thudng, Idng t u y i n h i u h i t khdng ed djch tiit, t i bao khdng tdng sinh, khdng thoai hod, md dem khdng tang sinh, khdng sung huyit. Mpt s i it t u y i n trong long ed hing c i u , md dem c6 sung huyit nhe. K i t qua nay cho t h i y hinh thai t u y i n binh thudng nhung c6 sung huyit nhe m6 dem (hinh 4),

Quan sat vi t h i tuyin t i i n liet cua chudt 16 5 (TLA3g/kg) t h i y da s i cac nhdm tuyin tuang d i i d i u , khdng cd ton thuang t i bdo vd md. M6t s i tuyin trong Idng cd chua djch, md ke sung huyit vd phu n i , kh6ng tdng sinh, kh6ng xdm nhap viem. K i t qua ndy cho t h i y hinh anh tuyen tien liet tuang tu nhu hinh anh tuyin tiin liet ehu6t 16 3,4 Id hinh thdi tuyin binh thudng nhung cd sung huyit, phu n i md ke muc d6 vua (hinh 5).

17

N g h i e n CCFU - Ky t h u a t

• . • ' . • • . , . 5

Hinh 1: Ciu tmc vi thi TLT chudt Id 1 (HExlOO) 1- T4 bao bieu mo tuyin; 2- Long tuy4n: 3- M6 ke

Hinh 2: C l u fnvc w f/ii TLT chudt Id 2 (HExlOO)

^•^p

• > i ' J • • • ' - • ' • • ^ . > ^ > ' ^ , • , " • , ; ?

,^->-5 '.

4

,• V

Hinh 3: Cdu tnjc vi thi TLT chudt Id 3 (HExlOO)

f

^ 5 / ;r >«:»i^ 1 ' ' ' . ' Hinh 4: Cdu tnJc vithi TLT chudt Id 4 (HExlOO)

rH ^{• i ^ ;}

t x \ . J ^ - ^ . ^ ^ •••; V*

. / •

%

Hinh 5: Ciu tnJc vithi TLTchudtId 5 (HExlOO)

Ban luan

Trong c a the d u d i s y xuc tdc cua 5a- reductase, testosteron bj chuyen hda thdnh dihydrotestosteron ed hoat tinh manh han, hai c h i t ndy gdp p h i n vdo s y phdt trien gay phi dai t u y i n t i i n liet. Trong nghien cuu ndy chung tdi tiem testosterone Iiiu100|.ig/100g t h i trong chudt t h i y trpng lugng trung binh tuyin tiin liet chu6t 16 2 da tang 133% so vdi 16 ehung (p

< 0,001) k i t qua ndy cung tuang t y nhu cua 06 Trung Ddm (2003) tang 282% '^', Nguyin Thi Tan (2007) tang 231,25% '®'. D i i u ndy cho thiy cd the dp dung phuang phdp ndy d i nghien cuu s y anh hudng cua cac t h u i c len sy phat then tuyen t i i n liet .

0" Id 3 chupt vua tiem testosteron nhung d i n g thdi dung dutasterid (40|.ig/100g ) trpng lugng t u y i n t i i n liet giam 55% so vdi Id 2 chi dung testosteron (p < 0,001). Sa dT ed su giam trpng lugng t u y i n liet liet d cdc chupt 16 3 la do ditastend uc e h i ehpn Ipc 5 a -reductase nen 1dm giam dihydrotestosteron '^ *'). Tuang tir nhu vay trpng lugng t u y i n t i i n liet d cac 16 dung d i n g thdi ca tiem testosteron vd uing thuy long i m liiu 9g/kg vd 3g/kg t h i trpng cung lam giam tuang ung Id 2 4 % vd 20% so vdi 16 2 vdi p <0,05. S y giam trpng lugng tuyin tiin liet cua cdc chupt dung trd tan thuy long am kern han so vdi 16 dung dutasterid (p < 0,05).

K i t qua nghien cuu tren gdp phin chung minh tdc dung c h i n g phi dai Idnh tinh tuyin liet cua bai thuoc thuy long am. Tuy nhien, mot cau hdi dugc ddt ra tai sao trd tan thuy long am c6 tac dung giam trpng l y g n g t u y i n t i i n liet tuang ty nhu ditasterid nhyng y i u hgn, cd phai Chang thuy long am cung y c che 5a-reductase hay Id cd c a c h i khde hay cd nhiiu co che cung mpt lue?

18 TAP CHi DUQC HQC - 11/2009 (SO 403 NAM 49)

Nghien

CLPU

- Ky thuat

Theo YHCT thi phi dai Idnh tinh tuyen tien li$t thudc v i "Idm chyng", "Idm be", "long b i " vd dudng nieu t i c trd Id nguy&n nhdn chinh cua benh, Thuy long i m Id bdi t h u i c bao g i m 10 vj, vdi edng dung chinh Id: hoat huyit thdng kinh, hanh khi khai u i t , Igi thuy thdng Idm, nhuyin kien tan k i t nen lam m i m ca, giam viem. Qua phdn tich cho t h i y bai t h u i c ed vuang b i t luu hdnh, ty giai, mdc th6ng, b i i n xuc, nguu t i t , tang phieu dieu c6 tdc dung c h i n g viem. Tdc dung c h i n g viem cua TLA dugc chung minh trong mpt nghien cuu thuc nghiem khde cua chung tdi. K i t qua cho t h i y : trd tan thuy long i m liiu 5g/kg/ngdy vd 15g/kg/ngdy trong 7 ngdy, uc e h i sy phdt then u hat tuang ung la 23,09% vd 20,65%, giam phan ung phu viem c i p 34% so vdi 16 ehung vdi s y khde biet ed y nghTa thing ke '^'. Cd the do lam giam viem nen TLA gdp p h i n Idm giam trpng lugng t u y i n t i i n liet, tdng cudng dinh duang cho t u y i n t i i n liet vi vay md Idm cai thien t i i u tien, tranh u t i e t i i u tien d benh nhdn phi dai Idnh tinh tuyin t i i n liet tren Idm sang vd thyc nghiem. Trong nghien cuu ndy chung toi chua c6 d i i u kien ehung minh lieu TLA c6 uc c h i 5 a-reduetase hay khdng. O i tra Idi edu hdi nay c i n t i i n hdnh cac nghien cuu sau t i i p theo.

Kdt luan

Nghien cuu tdc dung cua trd tan thuy long i m d i i vdi phi dai Idnh tinh t u y i n tien liet tren thyc nghiem d chudt edng trlng b l n g testosteron 100|.ig/100g the trpng cho k i t qua nhu sau:

- Sau 7 ngdy nghien cuu, thuy long am liiu 9g/kg vd 3g/kg t h i trpng cd tac dung Idm uc c h i s y tdng trpng lugng t u y i n t i i n liet. Tdc dung giOa hai liiu Id tuang duang nhau.

- Trd tan thuy long i m khdng Idm thay doi Idn tdi c i u true vi t h i t u y i n t i i n liet cua chudt.

S u m m a r y

"Thuy long am" (TLA) has been commonly used to treat benign prostatic hyperplasia.

Herein, the effects of TLA on benign prostatic hyperplasia in male rats was investigated. The treatment course were 7 consecutive days.

Rats were divided into 5 groups: group 1 was given pure water orally and all the rest (group 2, 3, 4, 5) - subcutaneous injection of testosterone

at dose of 100fjg/100g body weight Group 3 was added dutasterid at dose of 40pg/100g orally, group 4 and 5 - TLA at dose of 9g and 3g/kg/day, respectively. The result showed that the weight of prostates of rats in group 2 was significantly greater than that in group 1 (133%o).

the weight of prostates of group 4 and 5 decreased by 24%, and 20%o in comparison with group 2 (testosteron-injected). The changes in prostate weight were not remarkable between group 4 and group 5. After 7 consecutive days of taking TLA, no morphologic damages on microscopic prostates images were seen.

Key words: Thuy long am, benign prostatic hyperplasia.

T a i lieu t h a m k h a o

1. Trin Lap Cong, Trin Thanh Tung, Banh Van Khuu, Nguyen Trong Thong, Nghien cuu tac dung ching viem cua tra tan thuy long am tren thuc nghiem. Tap chi Duac hoc s i 4, tr. 18-22, (2009).

2. Bertram G. Katzung, The gonadal Hormones and Inhibitors. Basic and Clinical Pharmacology, 10th edition, Chapter 40, (2007).

3. Do Trung Dam va cong su, Xay dung mo hinh gay phi dai tuyen tien Net a chuot cong tring de nghien cuu cao nang hoa tring, Tap chi Duac lieu, tap 8, s6 6.tr. 173-176, (2003)

4. Trin Due Hoe, D6 Xuan Bang , Diiu tra dich t i hoc u tuyen tien li^t a nam gidi tu 45 tuoi tra len, De tai cap bo, tr 5-38, (1995)

5. Sarah Walfensohn & Maggie Lloyd, Small labolatory animal. Handbook of labolatory animal Management and Welfare, pp. 184-185, (1998)

6. Nguyin Thi Tan, Vu Thi Ngoc Thanh , Nghien cuu tac dung cua bai thuic tiin liet thanh giai d i i vdi phi dai lanh tinh tuyen tien liet tren thuc nghiem a chupt cing tring. Tap chi Duac hoc s i 10, tr. 16-20, (2007)

7. Nguyin Buu Thiu , Nhijng kha nang lua chon trong dieu tri phi dai lanh tinh tuyin tien Net. Ngoai khoa. 5: 1-7, (1997).

8. Truang dai hoc Y Ha Noi , Bo mon Duac ly, Duac ly hoc lam sang, Nha xuat ban Y hoc, tr. 607- 608 (2005).

9. Vien Duac lieu , "Nghien cuu cay nang hoa tring (Crinium asiaticum L. Amaryllidaceae) lam thuoc chOa phi dai tuyen tiin Net", Ky y i u cong trinh nghien cuu khoa hoc va cong nghe 2001-2005. NXB KH&KT. Tr.72-73, (2006).

10. Gia Hai Hoa, 'Tslghien cuu lam sang chung tien liet tuyin tang sinh", Vien nghien cuu Trung y, Trung Quic, (1995).

TAP CHi DUQC HQC - 11/2009 (SO 403 NAM 49) 19