TNG QUAN V HOMOCYSTEINE MU, TNG HUYT P

V TAI BIN MCH MU NO

*

ThS. Nguyn c Hong*, PGS. TS. Hong Khnh**

S Y T Tha Thin Hu, **i Hc Y Khoa Hu
1. M U

Tai bin mch mu no (TBMMN) l nguyn nhn gy t vong ng hng th 3

sau ung th v cc bnh tim mch. T l bnh nhn b TBMMN mt s nc gim r
do khng ch c huyt p ng mch, nhng nhiu nc t l TBMMN vn ngy
mt tng [2]. Nu mch mu no b v, TBMMN th xut huyt (XHN). Nu mch mu
no b tc, TBMMN th nhi mu (NMN) [1].
C nhiu yu t nguy c (YTNC) gy TBMMN, ngoi cc YTNC kinh in nh
tng huyt p (THA), i tho ng (T), bnh tim mch, bo ph, ht thuc l... Gn
y cc tc gi ni ting Anh cp kh nhiu. l tng Homocysteine (Hcy) mu,
mt YTNC ca THA v TBMMN [3]. hiu r hn vn ny chng ti i su phn
tch Hcy l g? Cng thc ho hc nh th no? C ch gy bnh v mt s nghin cu
lm sng v tng Hcy mu?
2. HOMOCYSTEINE
2.1. Homocysteine l g?
Nm 1932, Hcy ln u tin c m t bi Butz v Vigneaud. Hcy thu c t
sn phm c c axt nc tiu khi ang iu tr methionine (Finkelstein JD. 2000).
Nm 1962 Hcy c nhn din trong nc tiu mt vi a tr chm pht trin
tinh thn (Gerritsen T et al., 1962). Mt vi nm sau , ngi ta xc nh rng Hcy
tng rt cao trong nc tiu v trong mu nhng bnh nhn thiu ht trm trng v mt
di truyn Cystathionine Beta-Synthase (CBS) (Mudd SH, 1964). Cc bnh nhn thiu ht
v mt di truyn ny c xc nh c cc ng mch b x cng sm v huyt khi
tc mch. Trn 50% bnh nhn ny b bnh tim mch ti pht v vo khong 25% cht
trc tui 30 (Gibson JB, 1964) [7].
Nm 1969 McCully m t bnh l mch mu nhng bnh nhn ny, bao gm
s gia tng nhanh c trn, tin trin ca hp ng mch cnh, v s bin i ca cm
mu. Cc nghin cu dch t hc chng minh c s kt hp ph bin gia mc tng
Hcy mu trung bnh vi bnh mch mu, cng nh cc bin chng ph n mang thai,
cc thiu st ng thn kinh, cc thiu st khc tr s sinh, cc ri lon thn kinh tm
thn khc, lin quan n s sa st nhn thc ngi ln tui v gia tng t l t vong [7].
2.2. Cu trc phn t ca Homocysteine
Hcy l mt amino axit c cha sulfur trong cu trc phn t, c to thnh t qu
trnh kh methyl ca methionine. Trong mu, phn ln Hcy gn vi protein to thnh
protein-Hcy disulfide, phn cn li dng t do. Mt phn Hcy t do b oxy ho trong
mu to thnh Hcy-cysteine disulfide v Hcy-Hcy disulfide. Nh vy, Hcy ton phn
trong mu bao gm: Hcy gn proteine (proteine-Hcy disulfide) v Hcy t do (Hcy, Hcycysteine disulfide) [5],[15].

NH2
Albumin-S-S-CH2-CH2-CH
COOH
Protein-Homocysteine disulfide

NH2
HC-CH2-CH2-SH
COOH
Homocysteine

NH2
NH2
NH2
NH2
HC-CH2 -CH2-S-S-CH2-CH
HC-CH2-CH2-S-S-CH2-CH2-CH
COOH
COOH COOH
COOH
Homocysteine-cysteine disulfide

Homocysteine

2.3. Homocysteine trong mu

Hcy mu c nh lng di dng Hcy mu, c o lc i hoc sau khi ung
methionine.
* Hcy mu c o lc i (nhn i qua m t nht 12 gi):
Theo mt s tc gi, Hcy trong mu lc i khong 5-15 mol/L. Da trn Hcy
mu lc i, tc gi Khang v cs. phn chia tnh trng tng Hcy mu thnh 3 mc [4],
[5],[9],[11],[15].
- Mc tng va (Hcy t 16 n 30 mol/L)
- Mc tng trung gian (31 n 100 mol/L)
- Mc tng nng (> 100 mol/L)
** Hcy c o sau khi ung methionine:
Hcy mu cn c th c o t 4 n 8 gi sau khi ung methionine vi liu 100
mg/kg. ngi khng c bnh ng mch vnh, Hcy mu sau ung methionine l 39 +
12,8 mol/L (trung bnh cng + lch chun). Bng phng php ny, Hcy c gi l
tng trong mu khi n > trung bnh cng + 2 lch chun. Trong hai cch o va nu
trn, o Hcy mu lc i thng c s dng nhiu nht trong cc nghin cu v Hcy.
Khi nghi ng c ri lon chuyn ho Hcy mu m lc i ca n bnh thng th ngi ta
o Hcy sau ung methionine [5],[9].

Trong chu trnh ti methyl ho, Hcy kt hp vi nhm methyl (t N5-methyltetrahydrofolate) to thnh methionine, phn ng ny do enzyme methionine synthase
xc tc. Vitamin B12 mt ng yu t quan trng ca enzyme methionine synthase, axit
folic c vai tr to thnh tetrahydrofolate, cn enzyme methionine synthase v N5, N10methylenetetrahydrofolate reductase l cht xc tc ca chu trnh ti methyl ho. Khi
methionine trong c th tng cao qu mc hoc khi c th cn tng hp cysteine, Hcy s
chuyn ho theo con ng chuyn sulfur. Trong qu trnh ny, Hcy kt hp vi serine
to thnh cystathionine, phn ng ny do enzyme CBS xc tc, v hot ng ca enzyme
ny ph thuc vitamin B6. Sau cystathionine b thu phn to thnh cysteine.
Cysteine tham gia vo qu trnh tng hp glutathione hoc chuyn ho thnh sulfate ri
c bi tit qua nc tiu [3],[9].
2.4. C ch sinh l bnh tng Homocysteine mu [4],[5],[9]
Qua bng chng thc nghim bnh sinh x cng ng mch c xu hng phi hp
vi tng Hcy mu do ri lon chc nng ni m v tn thng tip theo s hot ho tiu
cu v hnh thnh huyt khi. Nghin cu trn ngi v ng vt chng t Hcy gy ra x
cng ng mch do s kt t tiu cu v hnh thnh huyt khi ni m tn thng.
Harker v cs. ngh Hcy lm lp ni m tn thng bc l c cht di ni m v
hot ho tiu cu. Len v cs. chng minh n king gy tng Hcy loi linh trng lm
tn thng iu ho vn mch v chc nng khng huyt khi, cc pht hin ny cng
c ng h trong nghin cu ca Celermajer v cs. chng minh gin mch l thuc ni
m. Van den Berg v cs. chng minh tn thng chc nng ng mu ni m bnh
nhn tr tng Hcy v bnh l mch mu ngoi bin.
Hcy nhanh chng t oxy ho khi Hcy mu tng, hn hp disulfides v Hcy
thiolactone c nh hng ln bao gm superoxide v hydrogen peroxide (theo cng vi
gc hydroxyl) c bit lin quan n nhim c mch mu do tng Hcy. C nhiu bng
chng rng ri Hcy gy tn thng t bo ni m phn ln do hydrogen peroxide. Harker
v cs. ngh trung gian gy tn thng t bo ni m do hydrogen peroxide di c
cht v t bo c trn ln lt qu sn v y nhanh s hot ho tiu cu v bch cu.
S oxy ho t ng to ra nhng dng oxygen c t bo khc bao gm gc anion
superoxide v gc hydroxyl. Superoxide ph thuc hnh thnh gc hydroxyl cho thy
khi u peroxyt ho lipid, nh hng xy ra mng bo tng ni m v phn t
lipoprotein trng lng phn t thp. S oxy ho t ng Hcy a n oxy ho LDL qua
gc superoxide anion pht sinh. Hcy thay i phenotype khng huyt khi bnh thng
ni m qua tng hot ng yu t V v c ch hot ng protein C, c ch
thrombomodulin, gy ra yu t m v ngn chn heparin sulfate. Tt c nh hng ny
thc s to d dng hnh thnh huyt khi v to prothrombotic bao quanh.
S sn xut nitric oxide t ni m cng nh hng bt li do Hcy, cc t bo ni
m bnh thng kh c Hcy bng phng thch nitric oxide kt hp vi Hcy vi s hin
din ca oxygen to ra S-nitrosohomocysteine. Nitro ho mt nhm sulfhydryl ca Hcy
c ch sulfhydryl l thuc pht sinh hydrogen peroxide. S-nitrosohomocysteine cng c
ch mnh tiu cu v gin mch. Hcy y mnh peroxyt ho lipid m c th k n l
gim nitric oxide synthase ni m v trc tip lm gim st nitric oxide.

C ch Homocysteine gy huyt khi x va ng mch

Hcy cng gy tn thng trc tip c cht mch mu do nh hng sinh hc v
chc nng sinh tng hp t bo mch mu. Hcy thiolactone, phn ng mnh vi cc sn
phm ph oxy ho Hcy, kt hp vi lipoproteine trng lng thp to thnh mt hn hp
thu ht thc bo mng ni mc v kt hp vi t bo bt trong mng x va mi sinh.
2.5. Cc nghin cu lm sng tng Homocysteine mu trong tng huyt p v tai
bin mch mu no
Nhiu nghin cu tng lai v nghin cu hi cu cho thy rng tng Hcy mu
trung bnh l YTNC tim tng c th thay i c do huyt khi tc mch, c bit
TBMMN. C s tng quan thun c ngha thng k gia Hcy mu v tt c cc th
TBMMN, c lp vi thuc l, cholesterol mu v p lc mu khi nghin cu tng lai
500 bnh nhn TBMMN v nghin cu hi cu 1.000 bnh nhn TBMMN gn y [10].
Nghin cu ca Hiroyasu Iso v cs. (2004), nghin cu tng lai, bnh-chng ca
11.846 ngi tnh nguyn tui t 40 n 85 Nht. Kt lun tng Hcy mu c kt
hp vi s gia tng nguy c cc th TBMMN, c bit nhiu TBMMN th nhi mu v
nhi mu l khuyt, trong s c nam v n Nht.
Nghin cu ca tc gi Ningjun Li & cs. (2002), nghin cu v gii phu bnh cu
thn nhng bnh nhn tng Hcy mu i n kt lun rng: Tng Hcy mu l YTNC
quan trng gy bnh do tn thng cu thn gy THA, c lp vi p lc mu[13].
Nghin cu ca Regina v cs. (2002) kt lun rng: THA nhng ngi thanh nin
va kt hp folate mu thp v Hcy cao v c hin din khng insulin hn so vi
nhng ngi thanh nin bnh thng. Nghin cu cho thy THA nhng ngi tr c th
l mt phn ca s biu hin sm ca hi chng khng insulin, ri lon folate v
chuyn ho Hcy mu c th ng vai tr trong cc giai on sm ca THA [14].
Nghin cu ca Coen v cs. (2003), nhiu nghin cu lm sng v dch t hc
cho thy mi lin quan gia Hcy mu v p lc mu c bit HATTh. Nghin cu dch t
hc vi quy m ln v tin hnh mt cch cn thn a ra kt lun rng c tng mi 5
mol/L Hcy mu kt hp tng HATTh v HATTr tng ng nam l 0,7/0,5 mmHg v

n l 1,2/0,7 mmHg c lp vi chc nng thn v nng vitamin mu. Thm vo ,

quan st cho thy rng khi iu tr liu php acid folic th lm gim Hcy mu ko theo
lm gim p lc mu, chnh v th c mi lin quan gia Hcy mu v p lc mu. Hcy
mu gim thp bng cch b sung acid folic qua thc n. C ch c th c gii thch
rng c mi tng quan gia Hcy mu v p lc mu bao gm Hcy mu gy ra hp cc
ng mch nh, ri lon chc nng thn, gia tng s hp th natri v x cng ng
mch[8]. Nghin cu ca Ahamad Hassan v cs. (2004), nghin cu dch t hc i
n kt lun rng tng Hcy mu c kt hp vi THA, xc nh c ngha thng k (p
= 0,002)[6].
3. KT LUN
C nhiu YTNC gy THA v TBMMN c pht hin, trong c YTNC va
mi l din l Hcy mu. S chuyn ho ca Hcy mu c lin quan n axit folic,
vitamin B12 hoc vitamin B6. V vy, khi c th thiu cc cht ny (nguyn nhn thng
do dinh dng) th Hcy mu s tng. Theo Selhub (2003), hai phn ba cc trng hp
tng Hcy mu c lin quan n tnh trng thiu t nht mt trong cc vitamin ny. Vic b
sung axit folic, vitamin B12 v vitamin B6 c th a Hcy mu v mc bnh thng[5],[9].
Ngi ta c th d on kh chnh xc nguy c t vong da trn hm lng Hcy trong
mu, iu m ngi ta khng th lm c nu ch da vo nng cholesterol [3].
X va mch mu do tng Hcy mu c lin quan n ri lon chc nng ni mc,
km theo s bin i cc yu t ng mu. Tng Hcy mu c thit lp nh mt
YTNC quan trng cho bnh bt tc mch mu [12].
TI LIU THAM KHO
TING VIT
[1]. Phm Gia Khi (2004). Tai bin mch mu no ti Vin Tim Mch Hc Vit Nam. Y
Hc Vit Nam, trang 17- 20, 2004.
[2]. Nguyn Ph Khng, Nguyn Oanh Oanh, Hong Trung Vinh, Nguyn Phi Nga
(2004). Mt s c im t qu no ti khoa tim mch bnh vin 103. Y Hc Vit
Nam, trang 12- 16, 2004.
[3]. L Xun Long, H c Hng, Phm Hong Phit, L Xun Trung (2002).
Homocysteine Trong Bnh L Mch Mu No. Tp ch Tim Mach Hc Vit Nam, s
32, trang 39-44.
[4]. Cao Phi Phong (2002). Tng quan v chng tng Homocysteine trong mu v t
qu. W.W.W.Thankinhhoc.com.
[5]. ng Vn Phc, Phan Th Danh, Nguyn Hu Khoa Nguyn (2003). Homocysteine
v bnh ng mch vnh. Y hc thnh ph H Ch Minh. Hi ngh khoa hc k
thut ln th 20, trang 7-13.
TING NC NGOI
[6]. Ahamad Hassan, Beverley J. Hunt, Michael O'Sullivan (2004). Homocysteine is a
risk factor for cerebral small vessel disease, acting via endothelial dysfunction.
Brain. Vol. 127. No. 1, 2004, 212-219.
[7]. Christina Balander-Gouaille, Teodoro Bottiglieri (2003). Homocysteine related
vitamins and neuropsychiatric disorders. Stroke. Baylor University Medical Center
Institute of Metabolic Disease, 134-140.
[8]. Coen D.A. Stehouwer, Coen van Guldener (2003). Does Homocysteine cause
hypertension. Clin chem Lab Med 2003; 41 (11): 1408-1411.

[9]. George N.W, Joseph Loscalzo (1998). Homocysteine and Atherombosis. The New
England Journal of Medicine 338: 1042-1049.
[10]. Homocysteine. Net (2005). Both prospective and retrospective studies have shown
that high homocysteine levels, homocysteinuria and also moderately elevated
homocysteine levels, are potentially modifiable risk factors for thromboembolic
events, particularly stroke. New data on homocysteine and stroke, 2005.
[11]. John W. Eikelboom, Eva Lonn (1999). Homocysteine and Cardiovascular Disease:
A Critical Review of the Epidemiologic Evidence. American College of PhysiciansAmerican Society of Internal Medicine, 363-373.
[12]. Milosevic/- Tosic/ M, Borota J (2003). Hyperhomocysteine a risk factor for
development of occlusive vascular diseases. Med Pregl. 55:385-91.
[13]. Ningjun Li; Ya-Fei Chen; Ai-Ping Zou (2002). Implications of
Hyperhomocysteinemia inglomerular sclerosis in hypertension. Hypertension.
American Heart Association, 2002; 39:443.
[14]. Regina Kahleov, Daniela Palyzov, Karel Zvra (2002). Essential hypertension in
adolescents: association with insulin resistance and with metabolism of
Homocysteine and vitamins.
[15]. Ren Malinow, Andrew G. Bostom, Ronald M. Krauss (1999). Homocysteine, Diet,
and Cardiovascular Diseases. American Heart Association. Circulation, 99:178182.
Xin lin h a ch: BS. Nguyn c Hong, Khoa HSCC, BV. Hng Tr, TP. Hu. Tel. C quan:
054.557015, nh: 054.812914, Mobi: 0914091359.