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 T H A O DU'O'NG TYP 2
Nguyen Trong Tai*
Nguyen Thanh Thiiy*, , Nguyen Linh Toan***
T O M 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
S U M M A R Y
THE CONCERNTRATION OF SERUM I N T E R L E U K I N - 8 I N C R E A S I N G ASSOCIATED
TO DISORDER OF L I P I D PARAMETERS I N PATIENT W I T H 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. D A T V A N 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 t d 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 d y 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 m d gia tang do thffa can, beo phi nhat la lang dpng m d 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 m d san xuat nhy:
adiponectin, secreted frizzled - related prdtein 5 (SFRP 5), leptin, interieukin ( I L ) - 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 t d 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 . D o ! tu'dng n g h i e n 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$n xet: Cac chi sd trung binh ve can nang, vdng eo, vdng hdng, WHR, BMI d nhdm benh nhan DTD typ 2 cao hdn ro ret so vdi ngffdi binh thffdng (p<0,001).
3.2. Tiiay ddi ndng dd lipid mau 6 benh nhan OTO typ Bang 2. Nonq do mot so chi so lipid mau ciia nhom ngh
^ — ^ ^ ^ 0 6 1 tu'dng Chi sd ^ ^ ^ " ^ ^ ^ ^
Triqiycend (mmol/l) Cholesterol (mmol/l) HDL-C (mmol/l) LDL-C (mmol/l)
Ngu'di binh thirdng (n = 34) ( I ± . S D )
1,67 ± 0,63 4,43 ± 1,18 1,36 ± 0,45 2,24 ± 0,8
2
en ciivOTO typ 2 (n = 40) (•^ ± S D ) 3,55 ± 2,69 5,80 ± 1,16 1,01 ± 0,24 3,19 ± 0,82
P
<0,01
< 0,001
< 0,001
<0,001
Nh$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 s y 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 n h d I L - 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 s y 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 s y 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 v i j ^ 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 T H A M 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. 7 1 9 - 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.
