A BAO CAP TONC QUAN
Tham luan ve gdc tir do
GS. Phan Chuc Urn Hgi Thdn kinh hoc Viit Nam
Qua nhOng nghien cdu gan ddy, ngudi ta cang ngay cdng hilu rd hon v l vai trd quan trong cOa cdc gdc t i ; do trong chet te bao. Vay gdc t i ; do Id gi, chOng gay chet te bdo nhuthe nao vd cd vai tr6 g) trong cdc benh ?
Gdc tvdo la trang thdi cau trijc cue phdn turcd mdt di^n td\& d quy d^o dien turngodi cCing, trong khi cdc phdn tdcua h^ sinh hpe deu cd sddien tOrchan d Idp ngodi ciing. VI vdy gdc ti/do cd ddc diem Id Tcit kim on djnh, chung san sang phdn dng vdi phan tijr hoac nguyen tCr lan can, cho di hoac nh$n thgm m$t di0n tur d l hodn chinh quy dao di^n tiJr ngodi cCing cua minh.
Cd the phan loai cdc gdc tudo thdnh 3 nhdm:
(A) Cdc gdc ti;do oxygen, (B) gdc t i ; do Nitric Oxid (NO) vd (C) cdc gdc ti^do thOrphat do cdc q6ztif do nguygn phdt (A) va (8) gdy ra.
I. CAC etiC TUDO OXYGEN
Sinh vat khdng t h i duy tri 6dac sd sdng neu thieu oxygen du ehi trong mdt thdi gian ngan, vi vay oxygen lien tue 6dac cung cap eho cdc te bao qua cae he vi tuan hoan rdng Idn cua eo the.
Trong todn bd sd lupng oxygen eung cdp cho cae t l bao ed khodng 2% phdn td oxygen cd nang lupng thap nhat, dUpc gpi Id cdc phdn tdoxygen d trang thdi triplet.Tuy van cd sd dien td chdn d quy dao ngodi cung cua phdn td nhimg do d trang thdi triplet cho nen ehung cung cd tinh ehat nhu mdt gdc tudo: ehung nhdn them mdt dien td (e) thdnh gdc tU do superoxid O— | vd them mdt
vdi Hydrogen Peroxid (H^Oj) thdnh gdc tU do Hydroxyl | oHJcdtinhoxy-hdamanh.
superoxid peroxid hydropercwd 0 ^ | + ( H p ; - . 0 , + r 6 H l +0H- superoxid hydro peroxid hydroxyl Superoxid O- , hydro peroxid {Hp) vS hydroxyl OH duoc gpi la cac (oai oxygen ph3n dien tCf (e) thiJhai nOta thJnh peroxid (Oj^). Ket
hpp v6i 2H*, peroxid (o'~) thanh Hydrogen Peroxid (HPj). Superoxid I O - 1 ket hpp
28 IHAN KINH HOC VIET NAM I s d 12/2015
Ung ROS (Reactive Oxygen Species), con gpi la ba loai chat oxy - hoa (the three oxydant specie^
trong do hydroxyl la chat oxy-hoa manh. f
Website: horthankinhhocvietnam.com.f
BAO CAO TONG QUAN k.
II. GOCTUDO NITRIC OXID (NO) Nitric Oxid (NO) dUpc tao ra lien tue bdi cdc t l bdo bilu md eda mach mdu tU amino acid arginin dudi tdc dung cda enzym NOS (Nitric I Oxid Synthaza).
Ngodi ra Nitric Oxid (NO) edn dupc tao ra td nhieu ngudn khde nhU cdc ndron, cdc than kinh H dem, cdc day than kinh va cdc bach eau.
^ Nitric Oxid (NO) Id gdc tU do hit sdc cdn cho sU sdng, nd tham gta dieu hda nhieu ehde nang , sinh ly quan trpng: dieu hda trUcfng luc thdnh ,, mach, dilu hda huylt dp, dc ehi tiiu cau, phdn
Ung viem, dan truyen than kinh.
Nitric Oxid (NO) chi trd thdnh ddc t l bao khi ehung chuyin thanh 2 chat oxy - hda manh Id u Nitrogen Dioxid NO^ va Hydroxyl O H
-^ ONOOH N 0 + O - -*0N00-
<^^ Natricoxid superoxid peroxid peroxinitrousacid ONOOH (khdng ben vdng)-'[A'4] + {6H\
peroxinitrous add nitrogen dioxid hydroxyl
Pha khdi ddng ddi hdi phdi ed chdt oxi-hda manh nhU hydroxyl f o n l ' P'^^" "^9 ^"^
mdt acid iDeo ehua bao hda cua mdng te bao (LoH):
gdetUdohydroxylcdtinhoxy-hdamanhr^Hl'^y di mpt hydrogen eda phan tdacid beo chda bao hoa {Lx)H)taoragdetudolipid i o .
•Phadantruyen:GdctUdolipid Lo kethpp vdi Oj thanh gdc tudo lipid peroxid I i^ool-Gdc tu do lipid peroxid [ i^oo 1 ket hpp vdi mot acid beo chUa bdo hda khac (L,H) thanh gdc tU do lipid mdi (L,) vd Lipid Hydro peroxid (L^OOH), cU nhuthe thanh phdn dng ddy ehuyen cda eac gdc tudo Lipid d mang te bdo vd cua cdc peroxid-hda d mang te bao.
fi R + LoH -^ 2o + RH
(w Chitce^-hoaiiianh A d d beo chua bao hoa Gficlirdolipd
^^
III. CAC G 6 C TUDO T H U P H A T Phdn vtng day chuyin
Gdc tu do R phdn Ung vdi phdn td Idn can X tao thdnh gdc tudo mdi >\r.GdctUdomdi X lai phdn Ung vdi phan td Idn can Y tao ra gdc tU do mdi nda Id Yva cUnhUthIthdnh phdn Ung^day chuyen cd khi lan xa so vdi vj tri ban dau cua R:
R-\-X -»ff+X X + y - > X + 7 v v
Qud trinh Peroxid-hda Lipid dmang tebdo Khi phdn dhg ddy chuyen lan tdi mang ^ ixo, xuat hien phdn dng peroxide - hda lipid d mdng te bao.
Qud trinh peroxide - hda lipid mang te bdo gdm 2 pha: pha khdi ddng va pha lan truyen:
Website: hoithankinhhocvietnam.com.vn
•Sg;,
Goe tu do lipid
LOO] + L,H
-f 400
Lipid peroxid
i, + (LoOOH)
§" D. Lipid Acid beo Goe tu do Lipid
"0*^ peroxid chuabaoh6a lipid Hydropaoxid
i , +O2 GCctydoUpid
( L , O 6 ) LqMdpCTOxid
i,o6 + L2H ^ 4 + (LiOOH)
Lipid Acid beo Gdct^rdo Lipid pooxid ciiua bao hoa lipid Hydcopeioxkl S6 12/2015 I THAN KINH HOC VIET NAM 29
A BAO CAO TONG QUAN
Qud trinh peroxide - hda lipid lam thay ddi dp Idng (fluidity) eCia mdng te bap, dan tdi tieu mang
^ bao vdi nhung he qud sinh hpe nghiem trpng ddi vdi te bao. Qua trinh peroxide - hda edn xdy ra d eae protein eua kenh (channel protein) cung nhu cda phdn tCf van diuyln (earner protein) d mang te bao, dan tdi nhdng bien ddi ehuyen hda vd chet te bdo
IV. TIEM NANG TON THUDNG OXY - H 6 A P^
VA KHA NANG TU BAD VE CHONG OXY HOA A„
CDACOTHE
Cdc chat oxy hda Hydroxyl To H 1 ''^" tU^ ^ddc tao ra tU 2 ngudn: gdc tu do oxygen va goe tU do Nitric Oxid (NO). Chung tao ra tilm nang tdn thuong Oxy-hda P^cda cothl.
Rat may Id co t h i cung lien tue tao ra eac chat chdng oxy hda, hpp thdnh khd ndng tu ve ehdng Oxy - hda A^ {Antioxidative Defense Capacity). Trong dieu kien binh thudng cda cothe, P^ va A^ cdn bang nhau, do dd khdng xay ra chet te bao do chat oxy hda, dam bao su can bdng ndi mdi (homeostasis) cda cPthl.
V. KET LOAN 1. Co chdng gdctifdo ?
Chung ta khdng chdng gdc tU do ndi chung vi cd nhCfng gdc tu do rat can cho su sdng, nhu gdc tu do Nitric Oxid (NO), chung tham gia dieu hda nhieu chUc nang sinh ly quan trpng cda cothe.
Cdi md chung ta can ehdng la cdc chat oxy- hda nhat la chat oxy-hda manh nhu Hydroxyl [ O H ] ' nguyen nhdn true tiep cda chet te bdo.
2. Cd can du phdng cdc benh bang cac chiit chdng gdc tif do (ma thUc chat la cdc chat chdng Oxy-hoa) ?
30 THAN KINH HOC WET NAM I S(5 12/2015
Trong dilu kien binh thudng cua co ttie Tiem nang tdn thuong oxy hda P^ edn bdng vdi khd ndng tU ve chdng oxy hda A^ cho n§ri khdng can dung ede chat ehdng Oxy - hda d^
du phdng eac benh eua ca the.
3. Vay trong ^eu kien benh, khi tiem nang tdn thiTcmg Oxy - hoa P^ tang dot xuat, lam cho P^ vd A^ mat can bSng, cd can bd sung chat chdng Oxy - hda ?
* Trdn ly thuyet trong tinh hudng nay rS cdn bd sung chat ehdng oxy-hda d l bdo vk eac te bdo khdi bj chit va lue ndy chat chong oxy-hda ed vai trd eda chat bao ve te bao, vi du d nao chung ta Id cae ehat bdo ve than kinh (neuroprotection).
* Tren thUc te lam sang eho tdi nay chUa c6 chat chdng chat oxy- hda ndo cd tdc dung bdo v^
te bdo khdi bi chet (ke cd nhdng ehdt chdng oxy- hda cd tae dung bao vk t l bao tren thue nghiem),
De gidi thfeh mdu thuan gida ly thuyet - thi^c nghidm va thUc te lam sang, ngudi ta cho rdng oi nhieu nguyen nhdn gay ra chet te bao, gdc tUdo chi la mdt trong sd nhdng nguyen nhan dd cho nen khi ehdng chat oxy hda dem ddc, t l bao van nhanh ehdng bj chet bdi cae nguydn nhdn khac Vidu trong dot quy thiiu mau ndo, ngodi nguyer nhan chet te bao do gdc tU do (chat oxy-hoa), edn cd nguyen nhan kich thich ddc glutamat thieu mdu cue bd gdy thiiu oxygen va glucoza lam cho te bao mat nang lupng, khdng thUc hien dupc cdc chdc nang phu thudc nang luong nhii duy tri ede gradien ion qua mang t l bdo, gayra khd cue mang te bdo va tang ddng vao (influx) eua canxi qua cac k§nh canxi, kieh thich gii phdng eae chat dan truyen nhu glutamat dtan ciJng than kinh trude synap. Glutamat gan vio ede thu the d mdng sau synap, kfeh thfeh dong vao natri va canxi, gay ra ddng thdc bien ddi sir*
hda (phu ne te bdo, tdn thuong ty lap the, gdctu Website: hoithankinhhocvietnam.coi irrn
1
BAO CAO TONG QUAN k.
do, boat hda cac enzym proteaza, nucleaza v.v...) ddn tdi chet t l bdo. Dudi ddy la benh sinh chit te bdo do Glutamat:
i«l Hi
"i
i)>
lit diil ti
r ^
Thieu mau cue bpMat nang lupng
i
Khuci^c
i
Giai phdng Glutamat
i
^ , ^
i
jungli
M
%^
Ddng vao Na"^, Ca^"^
Phil te bdo / X^^Hogt hda cac enzym Ton thuong ty l^-p the Goe t\i do
1 •
C h l t t l b ^ (do chat kich thich - dpe glutamat)
Gida CO chl chit t l bdo do gdc tudo vd ca chl chit t l bdo do kich thich ddc td do glutamat cd mdi tuong quan chat che:
Hinh thanh goe tu do 1( A
V j - C a ^
^ - Hoat hoa cac enzym / phospholipaza, proteaza,
^ endonucleaza, nitric oxid Chgttebao synthaza...
Qua so do tren chung ta thay rd trong dot quy thieu mau ndo, sd dung chat chdng gdc tU do (chdng chat oxy hda) hoan toan khdng bdo ve dupc te bao khdi chet vi te bao se van bj chet bdi chat kfch thfeh ddc gutamat hoae bdi mdt chat ddc te bao nao khae ma ta ehia phat hien ra.
Ndi tdm lai hien nay trong phdng b§nh khdng can chat chdng gdc tu do (chong oxy-hda) vd trong dieu tn benh ehat chdng gdc tu do (chdng oxy hda) chua thdy cd tdc dung tren thUc te lam sdng. Hy vpng trong tuong lai, khi chung ta hilu sdu them ve gdc tu do, luc do cd t h i chat ehdng gdc tudo se khdng nhdng ed Ung dung hieu qud tren ldm sang, ma edn ed the ed nhdng phdt hien mcrt to Idn trong y hpe tuong lai.
m
0^'
0^
ien*
tha?
ifn.co Website: hoithankinhliocvietnam com.vn SC 12/2015 I TH/yi KINH HOC VIET NAM 31
