Tăng nồng độ IL 8 huyết thanh liên quan với tình trạng rối loạn lipid máu ở bệnh nhân đái tháo đường typ 2

Y HOC
VIET
NAM THANG 2 - SO 2/2014
TANG NONG DO
IL-8
HUYET THANH LIEN QUAN
Vai
TINH TRANG ROI LOAN LIPID
MAU
a
BENH NHAN
DAI
THAO
DU'O'NG TYP 2
Nguyen
Trong
Tai*
Nguyen
Thanh
Thiiy*,
,
Nguyen
Linh
Toan***
TOM TAT
Nghien cffu dinh
lUOng
ndng do IL-8 huyet thanh
va mpt so chi so lipid mau tren
d
40 benh nhan

dai
thao dddng (DTD) typ 2 so sanh
vdi
34 ngu'di khoe
manh.
Ket qua cho thay nong dp IL-8 huyet thanh,
tnglycerid,
cholesterol, LDL-C mau tang cao ro ret
6
benh nhan DTD typ 2 so
vdi ngUdi
khoe manh
(p<0,05). Trong
khi
do, nong dp HDL-C mau giam ro d
benh nhan DTD typ 2 so vdi
cJ
ngUdi khoe manh
(p<0,01). Nong do IL-8 huyet thanh c6
tifanq
quan
thuan
vdi
nong
Qg
cholesterol (r=0,35, p<0,01),
triglyceride
(r=^0,479,
p<0,001)
va LDL-C (r=0,397,

p<0,001) trong mau va co
ti/flng
quan nghich vdi
nong do HDL-C
(r=-0,286,
p<0,05) d benh nhan DTD
typ 2.
ket
qua nay cho thay tang cao mffc IL-8 huyet
thanh co
lien
quan vdi tinh trang rdi loan lipid mau 6
benh nhan DTD typ
2,
Tff
khoa;
type 2 diabetes, T2D, IL-8, lipid parameters
SUMMARY
THE
CONCERNTRATION
OF SERUM
INTERLEUKIN-8
INCREASING ASSOCIATED
TO DISORDER OF LIPID PARAMETERS IN
PATIENT WITH TYPE 2 DIABETES
The levels of serum interieukin 8 (IL-8) and blood
lipid parameters of 40 patients with type 2 diabetes
(T2D) and 34 healthy control (HC)
mduviduals
were

examined.
The result showed that the concentration of
IL-8,
tnglycerid, cholesterol and LDL-C were
sighnificant
increase in blood of patients
with
T2D in
comparison to HC subjects (p<0.05).
In
contrast, the
level of HDL-C was significantly reduced in patients
with
T2D
in
comparison to HC
(p<0.05).
In patients
with T2D, the IL-8 level was positive correlation with
cholesterol
(r=0.35,
p<0.01), triglyceride (r=0.479,
p<0.001) va LDL-C (r=0.397, p<0.001) concentration,
but inversely correlated to HDL-C level (r=-0.286,
p<0,05)
in
blood.
This
finding indicated that the level
of serum IL-8 increased association

with
disorder of
lipid parameters
in
patients with T2D.
*
Tr&dng Dai
hpc
YHa Npi
'* Dai
hpc
y Vinh
***
Hpc
vien
Quan y
Phan bien khoa hoc: TS, Ho Anh Sdn
I.
DAT VAN OE
Benh sinh
OTO
typ 2 la hau qua
eiia
qua
trinh tac dong qua lai phffc tap
ciia
sff khang
insulin va khiem khuyet tiet insulin; khong co
SLT
huy hoai te bao p mien

djch,
vdi sff tham gia cua
cac yeu to moi trffdng va yeu td
glen.
Mpt so
nghien cffu cho thay, phan
Idn
benh nhan DTD
typ 2 eo the trang beo nhat la beo bung (beo
trung tam), tinh trang
dy
thffa
mS
la yeu to
chinh gay de khang insulin, giam nhay cam
ciia
insulin vdi mo va te bao. Ngffdc lai, d benh nhan
the trang gay thi tinh trang giam tiet insulin
thffdng dffdc quan sat thay trong benh sinh DTD
typ 2. Hau qua
ciia
mo md gia tang do thffa can,
beo phi nhat la lang dpng md d npi tang thffdng
gan lien vdi de khang insulin, tang glucose mau,
roi loan chuyen hoa
lipid,
tang huyet ap, tinh
trang
tien
viem, tien tac mach gay ra nhieu

nguy cd benh ly khac nhau 5. Hien nay, mo m6
dffdc xem la mpt cd quan noi tiet va ehuyen hoa,
nhieu hormon do mo md san xuat
nhy:
adiponectin, secreted frizzled - related prdtein 5
(SFRP 5), leptin, interieukin
(IL)-l,
IL-6, IL-8,
IL-
18,
tumor necrosis factor anpha (TNF-
o),
adipsin,
resistin,
MCP-1,
PAI-1
da dffdc chffng
minh cd lien quan vdi rdi loan chuyen hoa, la cac
yeu td nguy cd
ciia
DTD typ 2, benh tim mach
IL-8 hoat dpng thong qua cac
thy
the dac hieu
tren be mat te bao, gay
kich
thfch dong tin hieu
eJAK (c-Jun
aminoterminal kinase) va
NF-KB

(nuclear factor-kappa B) npi bao lam tang cffdng
san xuat cac chat trung
gian
hoa hpc cua viem,
gay de khang insulin.
II.
OOI
TUOWG
VA PHU'aNG PHAP NGHIEN ClTU
2.1.
Do!
tu'dng nghien cu'u
Gom 74 ngffdi, chia thanh 2 nhdm:
Nhom ng&di binh th&dng:
3^
ngffdi btnh
thffdng,
ed BMI 18,5 - 22,9, nong dp glucose
mau ttnh mach
lijc doi
< 6,1
mmol/L,
cac xet
nghiem sinh hda ve chffe nang gan (ALT, AST).
than (urea, creatinin), cac chi tieu vie lipid
(cholesterol, HDL-C, LDL-C, triglyceride)
d
trong
Y HOC VIET NAM THANG 2 • SO 2/2014
gidi han binh thffdng. Khdng

mSc
cac benh dai
thao dffdng,
tim
mach, huyet ap va hoan toan
khoe manh tai thdi diem nghien
cffu.
-
Nhdm
binh: 40 benh nhan DTD typ 2 (trong do
CO
20 benh nhan DTD
b/p
2 beo phi va 20 benh
nhan DTD
b/p
2 khong beo phi). Benh nhan
&ifqc
chan doan DTD typ 2 theo
tieu
chuan
ciia
To
chffe
y te the gidi (2010); kh6ng chpn nhffng
benh nhan dang dieu tn bang insulin, benh nhan
suy gan, suy
than,
dang mac cac benh npi
tiet

anh hffdng den chuyen hoa glucid
2.2.
Phu'dng phap nghien cii'u
Phffdng phap nghien cffu mo ta cat
ngang,
so sanh cd dot chffng
Cac chi tieu nghien cu'u:
- Cac chi sd lam sang: Khai thac benh
sff, kham xet theo mau thong nhat; Tuoi,
gidi,
nghe nghiep, thdi gian bi benh; Khai thac cae
trieu chffng lam sang thffdng gap nhff: An
nhieu.
uong nhieu, khat nddc, tieu nhieu, met mdi, sut
can;
Xae dinh cac chi so nhan trac nhd: can
nang,
ehieu
cao, vdng bung, vdng eo; Xae dinh
cac chi so huyet ap toi thieu va huyet ap tdi da.
-
Cac
chi
sd
can lam sang: xet nghiem hda
smh mau (glucose, insulin, cholesterol,
triglycerid,
HDL-C, LDL-C) thyc hien thddng
qui Labo. Ojnh iddng nong dp IL-8 huyet
thanh dffdc thffc hien bang thff nghiem mien

djch gan enzyme (ELISA, enzyme-linked
immunosorbent assay), sff dung cac
kit
eua
hang Orgenlum, Phan Lan,
qui
trinh theo
hffdng dan
eiia
nha san xuat.
2.3.
Xff ly so
lieu:
eac sd lieu phan tfch
ham phi tham so sff diing bang thuat toan
non-para
metric Mann-Whitney test, chi binh
phddng test, so sanh tffdng quan tuyen tfnh
sff dung phan mem
SPSS15.1.
So sanh sff
khac biet thong ke cd y nghia khi p < 0,05.
III.
KET QUA
3.1.
Dac diem lam sang benh nhan DTD typ 2
Bang
1. Dac dlem
ve
chi sd nhan trac cua ddi tffdng nghien cffu

^^^ ^Ooi tiTdng
Chi
sd ^~~~~^^^^
Can nanq fkq)
Vonq bunq
(cm)
Vonq honq
(cm)
Chi so eo hong
(Whr)
Chi so khoi ca the (BMI)
Ngu'di binli
thifdng
(n = 34)
(JTiSD)
43,2
± 5,4
66,8
± 7,5
82
± 4,5
0,81
± 0,05
18,1
± 2,2
Benli
nhan OTO typ 2
(n = 40)
(iTiSD)
60 ± 9,8

77,6 ± 8,3
88,4 ± 6,7
0,88 ± 0,06
22,0
± 3,7
P
<
0,001
< 0,001
< 0,001
<
0,001
<
0,001
Nh$n xet: Cac
chi
sd trung binh ve can nang, vdng eo, vdng hdng,
WHR,
BMI
d nhdm benh nhan
DTD typ 2 cao hdn ro ret so vdi ngffdi binh thffdng (p<0,001).
3.2.
Tiiay
ddi ndng dd lipid mau
6
benh nhan OTO typ
Bang
2.
Nonq
do mot so chi so lipid

mau ciia nhom
ngh
^—^^^061 tu'dng
Chi sd
^^^"^^^^
Triqiycend
(mmol/l)
Cholesterol (mmol/l)
HDL-C (mmol/l)
LDL-C (mmol/l)
Ngu'di binh thirdng (n
=
34)
(I±.SD)
1,67 ± 0,63
4,43 ± 1,18
1,36 ± 0,45
2,24
± 0,8
2
en
ciiv
OTO
typ 2 (n = 40)
(•^
± SD)
3,55 ± 2,69
5,80 ± 1,16
1,01
± 0,24

3,19 ± 0,82
P
<0,01
<
0,001
<
0,001
<0,001
Nh$n
x6t:
Nong dp cholesterol, triglycerid va LDL-C tang cao d benh nhan OTO typ 2 so vdi
ngiTcfl
binh thu'dng (p<0,01).
Ngi/cfc
lai, nong do HDL-C
giam
ro ret d benh nhan DTD
tip
2 so
vdi
ngu'di
binh
thu'dng
(p<0,001).
Y HOC VIET NAM THANG
2 -
SO
2/2014
3.3. Thay
dd'i

nong do
interleukin-8
d benh nhan DTD typ 2
Hinh 1. Nong do IL-8 d benh nhan DTD typ 2 tinh chung (A) va
6
phan nhdm DTD typ 2 co
thffa can, beo phi va khdng thffa can beo phi (B).
IL-
8
(P
fl/
ml
)
]:-f.
•I'K
.
K
>;
JOD
;K
(A)
Ngu'di binh thu'dng BN
OTD
typ 2
(B)
filhan
xet; Nong do IL-8 tang cao ro ret
d
benh nhan DTO typ 2 tinh chung (A), cung
nhU

phan nhom
CO
va khong cd thira can beo phi (B) so vdi
ngUdI
binh thudng (p<0,001). Khong thay cd
sU
khac biet
ve nong dp IL-8 cua benh nhan OTO typ 2 cd
thiTa
can beo phi so vdi benh nhan khong cd
thCra
can
beo phi
(BJ
{p>0,05).
3,4. Mdi tu'dng quan cua IL-8 vdi nong do lipid mau d benh nhan OTO typ 2
Bang 4. M6I tudng quan cua nong dp IL-8 huyet thanh
vdi
mpt sd chi so lipid mau d benh
nhan OTO typ 2
IL-8
Tu'dng quan vdi
Cholesterol
(mmol/i)
Triglycerid (mmol/l)
HDL-C (mmol/l)
LDL-C (mmol/
0,479
0,397
<0,001

<0,001
I
,
liiiui/i;
I
ij,jji I
^\J,\j\Ji.
Nhan xet: Nong do IL-8 huyet thanh tffdng quan thuan vdi nong dp cholesterol, triglycerid, LDL-C
(r>0,350; p<0,01) va tffdng quan nghich vdi nong dp HDL-C (r=-0,286; p<0,05).
y
HOC VIET NAM THANG 2 -
SO
2/2014
IV. BAN LUAN
Cac nghien cffu gan day da cho thay cd sy
lien
quan mat thiet
ciia thya
can beo phi vdi
khang insulin va DTD typ 2. 6 ngddi
thya
can,
beo phi, cac te bao mo
mS
tang cffdng san xuat
cac acid beo chffa este hoa, glycerol, hormon,
cac cytokine nhd
IL-1,
IL-6, IL-8,
TNF-o,

MCP-1,
PAI-1 ,
lam giam bai
tiet
adiponectin, SFRP-5
hau qua lam gia
tinh
nhay
ciia
te bao doi vdi
Insulin va gay de khang insulin 5.
O
benh nhan
DTD typ 2, IL-8 da dffdc chffng
minh
cd lien
quan den ed che khang insulin, nhff thong qua
cac thu the te bao IL-8
kieh
thich ddng tfn hieu
cJNK (e-Jun
aminoterminal kinase) va NF-kB
(nuclear factor-kappa B) lam tang cffdng san
xuat cae chat trung gian hoa hpc
ciia
viem, gay
roi loan bai tiet va lam roi loan ti'nh nhay cam
ciia
te bao doi vdi insulin tff dd gay khang insulin va
DTO.

Hdn nffa, hoat hoa ddng tfn hieu
cJNK
va
NF-KB se lam tang cffdng san xuat cae protein
nhff chat ffc che ddng tfn hieu cytokin
(suppressor of cytokin signaling) va phan tff
INOS
(inducible nitric oxide synthese). Day cung la eae
protein dieu hoa npi te bao ed lien quan den ed
ehe khang insulin va DTO typ 2 3.
Theo nghien cffu
ciia
Straczkowski va CS.,
(2003) tren benh nhan beo phi roi loan dung nap
glucose cho thay nong dp IL-8 cd lien quan chat
che vdi tinh trang khang insulin
7.
Phii
hdp vdi
mot so nghien cuff khac nhff
ciia
Hernander va
CS (2005) 2, Seham A va CS (2006) 6, ket qua
cua chiing tdi cho thay nong dp IL-8 huyet thanh
d nhdm DTO typ 2
t5ng
eao rd ret so vdi ngffdi
binh thffdng (P<0,001), (Hinh
IA).
Mac

dii
khdng
CO sy khac biet ve nong dp IL-8 d ca hai phan
nhdm DTD typ 2 beo phi so vdi DTO typ 2 khdng
beo phi (p>0,05), nhffng ed sff tang cao ro ret so
vdi ngydi binh thffdng (p<0,001) (Hinh
IB).
Cac yeu to thffa can beo phi, tang huyet ap,
glucose
ni^u,
hpi chffng ehuyen hda,.,. la nhffng
yeu to cho thay co lien quan den benh sinh DTO
typ 2, Nghien cffu
eiia
ehiing tdi cho thay sy thay
doi rat ro ret
ciia
cac chi sd lipid mau d benh
nhan DTD typ 2 (cd beo hoae khdng) so vdi
ngffdi binh thffdng (p<0,05). 6 benh nhan OTO
typ 2 va thira can beo phi hau het co
roi
loan
chuyen hoa lipid mau nhff tang cao ro ret ndng
dp cholesterol, triglycerid va LDL-C va giam
HOL-
C so vdi ngffdi binh thffdng (p<0,01). Tinh trang
roi loan lipid mau
d b?nh
nhan OTO typ 2 cd lien

quan
ciia
nong dp IL-8 huyet thanh (bang 3.4).
Nhieu nghien cffu da chffng
minh
d benh nhan
OTO typ 2 cd sy roi loan ve eac chi so lipid mau
[1-3],
trong dd HDL-C dffdc coi la yeu to ed vai
trd chong
lai
sd tao thanh cac mang xd
vij^
dpng
mach.
Thffa can, beo phi sd tfch tu va sff tang
sinh
ciia
cac mo md, tang cddng oxy hda cac
chat beo lam tang cddng
giai
phong cac ester
chda bao hoa, rdi loan cae thanh phan lipid mau,
tang cffdng hoat hda eac te bao viem den mo
md,
tff dd gay tang cffdng tong hpp
giai
phdng
IL-8.
Nhffng thay doi nay d benh nhan OTO typ 2

nhat la nhffng trffdng hdp cd beo da cho thay ed
vai trd nhat dinh trong benh sinh
thii^
can beo
phi va OTO typ 2 [4,5,6,7]'.
V. KET LUAN
6
benh nhan OTO typ 2, nong dp IL-8 huyet
thanh tang eao rd ret so vdi ngddi khde manh
(p<0,01). Nong dp IL-8 cd tffdng quan thuan vdi
cholesterol, triglyceride, LDL-C va tffdng quan
nghich vdi HDL-C trong mau (p<0,05).
TAI LIEU THAM
KHAO
1.
Bremer A. and
Jialal
I. (2013), "Adipose Tissue
Dysfunction
in
Nascent Metabolic Syndrome",
Journal of
Obesity.
2. Hernandez
C,
et al. (2005), "Interleukin-8,
monocyte chemoattractant
protein-1
and
IL-10

in
the vitreous fluid of patients with proliferative
diabetic retinopathy",
Diebet
Med
22,
pp. 719-
722.
J.
Kahn SE, et
al.
(2006), "Review Article
Mechanisms linking obesity to insulin resistance
and type 2
diabetes".
Nature 444, pp. 840 - 846.
t.
Ning Dong, Bing Xu,
Bingsong
Wang,
Liqun
Chu.
(2013) "27 aqueous humor cytokines
in
patients
with
type 2 diabetes
with
or without
retinopathy".

Molecular Vision 2013; 19:1734-
1746.
5. Sandra
Galic,
et at. (2010), "Adipose tissue as
an endocrine
organ".
Molecular and Cellular
Endocrinology
3J6,
pp
129-139.
6. Seham A.
bou-Shousha,
Mona H.
Abd
El-
Megeed,
Hala
K. Sultan (2006), "Interieukin -
8, Ferritin and Soluble transfernn receptors in type
2
dibetes
mellitus".
The Egyptian journal of
immunology vol 13 (1), pp.
19
- 25.
7.
Straczkovi/ski M,

et al. (2003), "Plasma
interieukin 8 concentrations in obese subjects
with
impaired glucose tolerance", Cardiovasc
Diabetol2.