B Y T

TRNG I HC DC H NI

TH T NG

NGHI N C T C D NG C B

C Y C TR N T H NH

G Y R I N NG TRN

THNH CH

KH N T T NGHIP DC

H NI 2014

B Y T TRNG I HC DC H NI

TH T NG

NGHI N C T C D NG C B C Y C TR N T H NH G Y R I N NG TR N

THNH CH

KH N T T NGHIP DC

Ngi hng dn:

Ni thc hin:

N

H NI - 2014

N

PGS.TS.

ThS

Sinh vin

C C

T N ........................................................................................... 1

Chng 1: TNG QUAN ........................................................................... 2

1.1. T ng n c ............................................................................................... 2

............................................................................................... 2

1.1.2. Cc xt nghi ......................................................................... 5

1.2. Bnh ch i t ............................................................................. 6

ch. .................................................................................... 6

1.2.2. Ch y mu do ti u c u. ........................................................................................... 8

1.2.3. Ch y mu do cc y u t ...................................................................... 9

1 C c h nh nghi n c t c d ng c m mu. .................................................... 10

ch ................... 10

u c u ............................................................. 12

........................................................ 13

1.4. Cy Mc ................................................................................................................ 15

1.4.1. M t ................................................................................................................... 15

1.4.2. Phn b , sinh thi ................................................................................................ 15

1.4.3. B ph n dng ...................................................................................................... 16

1.4.4. Tnh v , tc d ng ................................................................................................. 17

1.4.5. Cng d ng ........................................................................................................... 17

Chng 2: I TNG PHNG PH P NGHI N C U ..................... 18

2.1. i t ng nghi n c ........................................................................................... 18

2.1.1. nghin c u ...................................................................................... 18

2.1.2. ........................................................................................... 18

2.1.3. .................................................................................... 18

2.2. Ni dung nghin c u ............................................................................................ 19

2 Phng ph p nghi n c u ..................................................................................... 19

ng c m mu c a b i lo mu .. 20

a b ......................................... 23

2 4 Phng ph p x liu ................................................................................... 24

Chng : THC NGHIM, KT QU V BN LU N ............................. 25

3.1. Kt qu nghin c u .............................................................................................. 25

3.1.1. Tc d ng c i lo ................ 25

3.1.2. Tc d ng c a b mc trn thnh m ch ................................................................ 33

3.2. Bn lun ................................................................................................................ 34

3.2.1.Tc d ng c m mu c a b i lo ................. 34

3.2.2. V tc d ng c a b mc trn thnh m ch ........................................................... 41

KT LU N KIN NGH ..................................................................... 43

TI I TH KH

D NH C C C K HI CH IT T T

ADP Adenosin diphosphat

aPTT Activated Partial Thromboplastin Time

ATP Adrenosin triphosphat

FDP

PPSB Prothrombin, proconvertin, stuart, antihemophilia B

PT Prothrombin Time

TT Thrombin Time

TXA2 Thromboxan A2

D NH C C C BNG

T n ng Trang

26

a

27

28

aPTT trn ng acenocoumarol

30

ng heparin

31

aPTT ng heparin

33

34

D NH C C C H NH

T n h nh Trang

y mc (Caryota mitis Lour., Arecaceae) 16

19

26

t

29

32

1

T N

N cy M

trn

1. nh gi tc dng cm mu ca b c c t n t h nh g i

lon ng u.

2. nh gi tc dng ca b cy mc trn thnh mch.

2

Chng 1

TNG Q N

1.1. T ng n c

pht

[4],[17].

1.1.1.1. Giai on thnh ch v vai t ca thnh ch

2

[4],[17].

1.1.1.2. To nt tiu cu

K

+

W

3

..

K

[4],[17].

1.1.1.3. To cc u ng

t

Giai on to oth o ina ha th o o a tin hot ng

- i sinh: c

-

++

++

- i sinh: q

++

z

[4],[17].

4

Giai on chuyn prothrombin thnh thrombin

z

[4],[17].

Giai on to thnh fibin

i

khng -

[4],[17].

1.1.1.4. Co cc u ng

K

++ ++

[4],[17].

1.1.1.5. Tan cc u ng

z

z

, [4],[17].

5

1.1.2

1.1.2.1. Xt nghi ca giai on c u an u

S ng tiu cu v ch c n ng tiu cu

K

collagen, ADP, acid arachidonic,.. [15],[17].

1.2.2.2. Xt nghi ng u

Th i gian u ng

[15],[17].

Th i gian thrombin (Thrombin Time: TT)

u [15],[17].

Th i gian prothrombin (Prothrombin Time: PT)

i calc .

6

K.

K [17].

Th i gian thromboplastin hot ho tng phn (aPTT)

[15],[17].

XI, XII, VIII, IX, X, V, II nn

K

[17].

1.1.2.3. Xt nghi giai on h n hu fi in

Sn phm phn hu fibrin (FDP)

K

F F ch.

F

[15],[17].

Th i gian phn gii euglobulin

X

t ho plasminogen.

[15],[17].

1.2. C c nh ch i t

do

1.2.1.1. Bnh R ndu-osler

-osler do ,

.

7

Trn l

-

[1].

1.2.1.2. Ch u do th tng c ch u d v

B , 8 %

t

[1].

1.2.1.3. Xut hu t do d ng- h i ch ng Scho in H noch

-

[1].

1.2.1.4. Xut hu t do nhi khun cp tnh

[1].

1.2.1.5. Thnh ch d v do thiu vita in C

.

.

C [1].

8

1.2.2.1. Bnh u nhc tiu cu G anz ann

[1].

1.2.2.2. Bnh t ng tiu cu ti n ht Th o oc t ic

33

[1].

1.2.2.3. Ch u do tiu cu to ha h i ch ng B na d-Soulier

.

[1].

1.2.2.4. Bnh Wi and

W

da

[1].

9

1.2 3

1.2.3.1. Ch u do thiu cc u t h thu c vita in K:

.

(prothrombin, proconvertin, stuart, antihemophilia B) [1].

1.2.3.2. Bnh H o hi ia

-

-

- -

-

-

- [1]

1.2.3.3. Bnh thiu fi inog n u inh

[1].

1.2.3.4. Ch u do thiu u t

K

K

K

10

vitamin K [1].

1.2.3.5. Ch u do cc cht c ch cc cht khng th o o a tin

Trn lm

[1].

1.2.3. . Bnh ca fi inog n

[1].

1 C c h nh nghi n c t c d ng c

,

gy

3

1.3.1.1. M h nh g t ng tnh th thnh ch

gu n t c

gy vim , prostaglandin, leucotrien gy gi

8 8

11

Tin hnh

- -

- %

sau, gy m c 8 8

% 8 8

ether.

nh gi

trong

-

l %

- I (%): %

- D0:

.

- D1:

1.3.2.2. M h nh nh gi tc dng ca thu c t n h ch tai th c .

gu n t c

Tin hnh

-

12

- .

K

nh gi

[3],[12],[16],[26].

gia .

1.3.2. M hnh

1.3.2.1. M h nh g gi ng tiu cu

M hnh gy gi m ti u c

gu n t c: h khng

Tin hnh

2.5-3 kg

-

- i sinh l .

- .

-

.

. i cng, tim

-GPIb, anti-IIb - u

nh gi

S ,

2].

13

1.3.2.2. M h nh g gi ch c n ng tiu cu

gu n t c

K

ADP v th

tham gia

z

thrombo

z

[8].

Tin hnh W

nh gi

[30].

1.3.3. M hnh

th

14

1.3.3.1. M h nh g i on ng u ng cc thu c khng vitamin K.

gu n t c enzym epoxid-reductase K-

K

W

K z -

[8].

Tin hnh

8

nh gi

[24].

1.3.3.2. M h nh g i on ng u ng ch ng ng h a in

gu n t c: b A

m

K A

An

[8],[17].

Tin hnh W 8

15

z

-

nh gi

[32].

.

1.4. Cy Mc

4

Caryota mitis Arecaceae.

-8

-

-

-

-

- -11 [10],[11],[13], [18].

4 ,

Caryota L. l

16

G i

5 c [13],[18].

Hnh 1.4: Cy mc (Caryota mitis Lour., Arecaceae)

(http://www.plantes-botanique.org/espece_caryota_mitis)

4 3 p

[10],[11],[13],[18].

Caryota mitis.

17

4 4 ,

[11],[13],[18].

4 5

[15]. Ngoi

- 12g [13],[18].

M t i thu c c c

-

- 8 8

8

16g, ngy 2 [10],[11].

-

5 ngy.

- au, sao

- .

- c

[13],[18].

18

Chng 2

I TNG PHNG PH P NGHI N C

2.1. i t ng nghi n c

2.1.1 N

cy m

Caryota mitis Lour., Areca

-700

% - 8% - % - % - %

2.1.2

-

-

2.1.3

-

- My li tm

- Heparin natri (Heparin 5000 IU -

-

19

-

-

2 2 Ni d ng nghi n c

-

.

-

2 Phng ph p nghi n c

Hnh 2.3.

Phng ph p nghi n c

p

aspirin

acenocoumarol

Tr

heparin

trn

mu

trn

mu

g trn

20

3

2.3.1.1 nh gi tc dng c u ca c c t n chu t g i on ng

u ng a i in.

nh hng ca b c n th i gian ch u t n chu t g i lon

ng u ng aspirin.

nhin thnh 3 l:

- g:

- ,

-

ng

, sau khi ,

0

y. So snh th i gian ch y mu

gi

%

:

A(%)

T0

T1

21

T %

cng th c (2):

%

T1 : th

T2

nh hng ca b c n tiu cu v m t s ch s ng u c n t n

chu t g i lon ng u ng aspirin.

- , cho

[31].

- l ng

my

l

2.3.1.2. nh gi tc dng c u ca c c t n chu t g i on ng

u ng ac nocou a o .

nh hng ca b c n th i gian ch u t n chu t g i lon

ng u ng acenocoumarol.

-

-

-

22

acenocoumarol

6g d

,

,

0

nh hng ca b c n th i gian ng u a TT T t n chu t g

r i lon ng u ng acenocoumarol.

- cho

[31].

- nh l

n .

2.3.1.3. nh gi tc dng c u ca c c t n chu t g i on

ng u ng h a in.

nh hng ca b c n th i gian ch u t n chu t g i lon

ng u ng heparin.

-

-

-

23

2

d . , sau

, c

0

giy.

nh hng ca mc n th i gian ng u a TT T t n chu t g

i on ng u ng h a in.

x ,

3

K

tai

K

0,05% - 0,08% - 0,1% - 0,5% - % m l i s gi t

ch y qua h m ch tai.

Ghi l i k t qu , so snh s gi t ch y sau khi thm

%

24

I(%)

N0

N1 sau k

2 4 Phng ph p x i

ng M SE (M

-

hi p < 0,05.

25

Chng

THC NGHI KT Q BN N

1 Kt nghi n c

3.1.1. T

heparin.

3.1.1.1. Tc dng c u ca c t n chu t g i on ng u ng

aspirin.

,..

Do aspirin z z

cyclooxygenase spirin gip

nh mng , lm ADP, nn aspirin gy

[8], [17]. D aspirin

qua

ng c a b n th i gian ch gy r i lo n

ng mu b ng aspirin.

K

26

ng 3.1: Tc dng ca c n th i gian ch u t n chu t g i on

ng u ng aspirin

L i Thi gi n ch (s)

n=10) - 80 4,12

nh (n=10) Aspirin 26 mg/kg 298 29,81

% t ng o vi

ch ng t ng

274,62

p p1

27

.- L

6g /kg

, t y mu 37,36%

ng k (p0,05

28

-

6g d

g

(p>0,05).

3.1.1.2. Tc dng c u ca c t n chu t gy i on ng u ng

acenocoumarol.

Acenocoumarol

[8],[17]. acenocoumarol

ng c a b n th i gian ch gy r i lo n

ng acenocoumarol.

K .

3 3 Tc dng ca c n th i gian ch u t n chu t g i on

ng u ng acenocoumarol

( p1 ): o vi ch ng t ng 2 o vi ch ng nh

L i Thi gi n ch ( )

n=17) - 114 10,09

nh (n=19) acenocoumarol 2mg/kg 208 21,28

% t ng o vi ch ng t ng 81,57

p p10,05

p2

29

(*): p

30

3 4. nh hng ca c n th i gian ng u T v a TT trn chu t

g i on ng u ng ac nocou a o .

( p1 ): o vi ch ng t ng 2 o vi ch ng nh

- L c acenocoumarol 2 mg/kg trong 5

i 57,43%, PT 157,69% aPTT 77,62%

(p

31

A

[8],[17]. V

ng c a b n th i gian ch gy r i lo n

ng heparin.

K

ng 3.5: Tc dng ca c n th i gian ch u t n chu t g i on

ng u ng h a in.

L

i

Thi gi n

ch ( )

n=17) - 114 10,09

nh (n=18) heparin 1200 IU/kg

367 33,40

% t ng o vi ch ng t ng 220,03

p p1

32

(*): p

33

ng 3.6: nh hng ca c n th i gian ng u T v a TT t n chu t

g i on ng u ng h a in.

L i Thi gi n

ng ( )

PT (s) aPTT (s)

(n=11)

- 444 9.5 7,8 0,2 21,0 1,0

(n=18)

663 21,7

8,6 0,4

78,7 15,0

% t ng o vi

ch ng t ng

49,32 10,27 274,76

p p1

34

thng qua

K [3],[12],[16]. K 7.

3 Tc dng ca c t n h ch tai th c

p

ringer

p

Ringer 55,2 1,5

DD % 52,8 0,9 4,35 p>0,05

DD 8% 45,5 0,8 17,75 p

35

30

n [32], warfarin

[22].

K

n. Tuy nhin

K

thu 7],[17]

ocoumarol, h

- thng

36

-

- chung.

-

K

17].

- Th

K

17].

a ch n oi ngu n iu v i u d ng:

- i

[19].

-

trn

[14]

[14].

.

3.2.1.2. Tc dng c u ca c t n chu t g i on ng u ng

aspirin.

h nh b

C collagen

37

z

z

A2

u. D

[8],[17]

.

K aspirin li 26 mg/

274,62%

37,02% . V

aspirin

tc dng ca c:

-

t

, 37,36%

/kg ng

.

,

ng

. T

g [7]. K

mc c dng

cc

- ti

38

mu . K cho

. K

3.2.1.3. Tc dng c u ca c t n chu t g i on ng u ng

acenocoumarol.

h nh: K K

K

K K

K

K vitamin K

z K- t K

[8],[17]

K

. K a

gy 81,57% 54,43%, PT

157,69% 77,62% .

N ma

. C

tc dng ca c:

- K

K t

acenocoumarol trong 5

ng 38,77%

K b

g acenocoumarol. K

K .

39

N hay

[7],[17]. K

K

- n

ng acenocoumarol

K

khng lin quan

3.2.1.4. Tc dng c u ca c t n chu t g i on ng u ng

heparin.

h nh: c A

m . Heparin

v Antithrombin III A

[8],[17]

h

220,03% 49,32%,

gian PT 10,27% 274,76%

ng k. N heparin

.

tc dng ca c:

-

40

30,16%

[7],[8

u

heparin.

-

K

aspirin,

K

heparin.

gian aPTT,

u v

Trong

.

[17

h.

41

3 mc trn

[6]

ng?

.

ch thng qua g

K [24]

8%

8% - % - % -

% % - 25,00% -

32,61% - 39,00%. V

K

16].

lm co cc

lm thnh

gy

ch. Cc m hnh ny ng cc tc nhn gy vim

histamin, leucotrien, ng m cc mao

[24]. K

thnh K n

[14].

.

42

.

43

KT N KIN NGH

1 Kt n

1.1. T

mu.

1.1.1 Tc dng c u ca c c t n chu t g i on ng u ng

aspirin.

- Aspirin gy ko

274,62% %

, (p>0,05).

- Trn

trong 5 n 37,36%

nh (p0,05).

1.1.2. Tc dng c u ca c c t n chu t g i on ng u ng

acenocoumarol.

- Acenocoumarol u 2 mg/kg

8 % 57,43% %, PT 157,69%

aPTT 77,62%

44

- gian aPTT:

1.1.3. Tc dng c u ca c c t n chu t g i on ng u ng

heparin.

- Heparin TDD

220,03% 49,32%, aPTT 279,76% 10,27%

i

-

30,16%

(p

TI I TH KH

1. Tr (1984), Phng ch ng chy mu -25.

2. c Bnh (2011), " ng c a tr li z n m t s ch

ng v t th c nghi m", Tp ch Y- Dc h c qun s , 4, tr. 1-7.

3. B c l c i h c H N i (2006), Th c t Dc

l, tr. 23-24.

4. B c l c - i h c H N i (2008), Gii phu sinh l,

NXB Gio d c, tr.77-88.

5. B mn Y h c c truy n i h c Y h c c truy n H N i (2008),

NXB Y h c, tr.204 (2008), Y h c c truy n

6. B Y t (2006), Dc h c c truyn, NXB Y h c.

7. B Y t (2006), Dc th Qu c gia Vit Nam.

8. B Y t (2007), Dc l h c, T p II, NXB Y h c, tr.113-117.

9. B Y t (2009), Dc in Vit Nam, T p IV, NXB Y h c.

10. T in cy thu c Vit Nam, NXB Y h c, tr.752.

11. T in th c v t thng dng, T p I, NXB Khoa h c v

K t, tr.590-592.

12. ghi n c u hc h i ch c n ng nh nh n

nh i u ng ch n o gi a au giai on c ng i Th ng ch

dng n o v in ch

i, tr.100-116.

13. Ph m Hong H (2000), Cy c Vit nam,, T -412.

14. Ph m Th Nghin c u tc dng ca cy mc trn th c

nghi th o hng lm thu c cm mu, Kha lu n t t nghi

i h c H N i, H N i, tr.21-50.

15. Isbiter James P., Harmening Pittiglio (1997), Hu t h c ng

, tr.14-21, 159-180.

16. ghi n c u tc dng cao nc Th thai t n

th c nghi v t ong i u t d a thai

-88.

17. Nguy n Anh Tr (2008), ng u ng dng trong lm sng

tr.10 - 210.

18. C thu c v ng v t thu c it a , T

K K 8 -284.

19. Vi c li u (2006), hng h nghi n c u tc dng dc l ca thu c

t tho dc, NXB Khoa h c v K thu t.

20. Beyazit Yavuz et al. (2010), " Evaluation of hemostatic effects of ankaferd as

an alternative medicine", Alternative Medicine Review, 15(4), pp. 329-336.

21. Bilgili Hasan et al. (2009), "Hemostatic efficacy of ankaferd blood stopper

in a swine bleeding model", Medical principles and practice, 18, pp.165-

169.

22. Blajchman M.A et al. (1979), "Shortening of the bleeding time in rabbits by

hydrocortisone caused by inhibition of prostacyclin generation by the vessel

wall", The american society for clinical investigation, 63, pp.1026-1035.

23. Bordeaux S. Jeremy et al. (2011), "Prospective evaluation of dermatologic

surgery complications including patients on multiple antiplatelet and

anticoagulant medications", J Am Acad Dermatol, 65, pp.576-83.

24. Cipil S. Handan et al. (2009), "In vivo hemostatic effect of the medicinal

plant extract Ankaferd Blood Stopper in rats pretreated with warfarin", Clin

appl thromb hemost,15(3), pp. 270-276.

25. Emre Huri et al. (2011), "The second step in vitro trial of Ankaferd blood

stopper: comparison with other hemostatic agents", Turk J Med Sci, 41(1),

pp.7-15.

26. Gerhand H. et al. (2002), Drug discovery and evaluation-pharmacological

assay, Springer, pp.305, 1053-1092.

27. Goker H. et al. (2008), "Haemostatic actions of the folkloric medicinal plant

extract Ankaferd blood stopper", The journal of international medical

research, 36, pp. 163-170.

28. Greene T.K et al. (2010), "Towards a standardization of the murine tail

bleeding model", Journal of thrombosis and haemostasis, 8, pp.2820-2822.

29. Khalifeh MR. (2005), "The management of patients on anticoagulants prior

to cutaneous surgery: Case report of a thromboembolic complication, review

of the literature, and evidence-based recommendations", American society of

plastic surgeons, 118(5), pp.110e-117e.

30. Kosar Ali et al. (2009), "The efficacy of Ankaferd blood stopper in

antithrombotic drug - induced primary and secondary hemostatic

abnormalities of a rat-bleeding model", Blood Coagulation and Fibrinolysis,

20, pp.185-190.

31. Rajasekaran Aijalu et al. (2010), Haemostatic effect of fresh juice and

methanoic extract of Eupatorium ayapana leaves in rat model, International

Journal of Biological & Medical Research, 1(3), pp.85-87.

32. Rustu Kose et al. (2012), "Hemostatic efficacy of folkloric medicinal plant

extract in a rat skin bleeding model", Dermatol Surg, 38, pp.760-766.

33. Sabatino Denise E. et al. (2012), " Progress

in molecular biology and translation science, 105,pp.151-209.

34. Sweetman Sean C BPharm, FRPharmS (2009), Martindale The Complete

Drug Reference, 36, Pharmaceutical Press.