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• TAP CHi NGHIEN CLPU Y HOC

TAG DUNG KHANG KHUAN CUA LOXAIN TREN INVITRO VA DIEU TR! BONG TREN MO HJNH B 6 N G O C H U Q T CONG TRANG

Tran Thanh T u n g \ Pham Thj Van A n h \ Nguyen Trong T h 6 n g \ Dao Kim Long^

'Sd mon Dwiyc iy - Truing Dai hoc Y Ha Ndi

^Cong ty Co phSn San xuat va Thutyng mat Nam YAurvini Che phim Loxain duv^ dung danh gia tac dung khang khuan tren invitro va tac dung dieu tn bong trSn mo hinh gay bong nhiet thwc nghiem. Tac dung khang khuan cua Loxain dwQC tien hanh tren Invitro, th&

tren 4 chung qu6c ti la Pseudomonas aeruginosa (ATCC 27853). Staphylococcus aureus (ATCC 25913), Escherichia coii (ATCC 25922), Klebsiella pneumoniae (ATCCBAA - 1705) ChudI cong trang chung Wistar ca hai giongdwc/c chia thanh 5 nhom. nhom 1 khong tac dong gi, nhom 2 - 5 dum gay bong nhi0t phia truv'C dui v&i kich thu^yc twang tu- nhau, sau do nhom 2 duuc boi dSu co 4 lan/ngay, 16 3 boisulfadiazln - bac 4 lin/ngay. Id 4 va 5 dwoc boi twang ung Loxain 4 lin/ngay va 6 ISn/ngay lien tuc trong 21 ngay. Sau do giit chuot. liy m§u da tai vSt bong de lam giai phiu b$nh Kit qua nghien cuv cho thiy Loxain nang do tw 0,025- 0,4g/ml khong &c ch4 4 chung vi khuin duuc thw Tren mo hinh gay bong nhiet thwc nghiem. O cac 16 dung Loxain thai gian hen khoi vet thu-ang bong diin ra nhanh, hieu qua diSu tn v4t thuxyng bong cua Loxain boi 4 lin/ngay va 6 ihn/ngay ia twang dwong nhau va twang duvng vai Id dOng sulfadiazin - bac trong 21 ngay ddu tri lien t{ic.

TO khoa: Loxain, tac dung khang khuin, chuot c6ng chung Wistar, bong nhiet tren da, li^n seo

I. DAT

V A N

DE

Bong la c h i n thu'ong thudng gap, co nhilu nguyen nhan gay ra nhu nhiet, hoa chit, phdng xa , , trong do bong do nhiet hay gap nhit, chiem to'i 84 - 94% tong sd nan nhan bong [1] Tuy myc dd bong ma benh nhan phai chju nhu'ng anh hyd-ng vdi nhung muc do khac nhau, benh nhan bdng thyd-ng phai dieu tri dSi ngay, tdn kem N l u d i l u tn khdng tot cd the se d l lai nhi/ng di chung lau dai cho ngydi benh lam anh hyo'ng den t h i m my, kha nang lao ddng, sinh hoat, tham chi gay t y vong cho ngydi benh

Dia chi !i§n he Tran Thanh Tung, BQ mdn Dupe ly, Truxyng Dai hoc Y Ha Noi

Email' [email protected] vn Ngaynh$n 02/3/2017 Ngay (JuK)C Chap thuan 25/4/2017

Hien nay, cd nhilu loai thudc dung de dieu tn tai c h i v l t thuang bdng dyoc san xult d"

trong nu'dc hoac nhap tCt' nu'dc ngoai 6' trong nude, mot so thudc y hoc c6 truyin da duoc nghien cuu, k l thya, dya tren ca so khoa hoc va dyac yng dung trong lam sang nhy cao va md' Maduxin tu cay sen, mat ong, Chitosan [2 - 6] Ben canh cac thudc y hoc cd truyin, cac chit khang khuIn, khang sinh dang duac SLF dung phd bien trong dilu tn tai chd v l t thuang bdng d nu'dc ta va tren t h i gidi nhy kem sulfadiazine - bac 1 % [7]

Cac thudc cua nude ngoai cd tac dung tyang d l i t i t nhung chi phi cao khong phu hop vdi dai bd phan benh nhan 6' nuoc ta ndi chung va benh nhan bdng ndi rieng Viec nghien cyu tim k i l m cac thudc mdi tu ngudn nguyen lieu trong nydc, cd try lyang doi dao, gia thanh khdng cao, tac dung dieu tn tai chd

TCNCYH 107 (2)-2017

(2)

T^P CHi NGHIEN CU'U Y HQC • v l t thuong bdng t i t van ludn dyac dat ra trong cdng tac dilu tn bdng

Loxain cd thanh phIn chu y l u la curcumin va p-caroten, dSy la hai hoat chit cd nhilu trong cu nghe va qua glc, nhyng loai cu, qua r i t pho bien d nude ta [3-caroten cd tac dung tang sCfC d l khang cua ca t h i , kich thich biet hoa t l bao bieu md, sinh tilt nhly [8] Curcu- min da dyac chyng minh cd tac dung khang khuan va nhanh liln seo Theo nghien ciru cija Mehrabani va cdng sy da chi ra curcumin dang kem 2% cd tac dung lam giam dien tich v l t bdng va nhanh liln seo tren md hinh gay bong nhiet tren chuot c i n g chijng Sprague- Dawley [9]

Dya tren ca sd dd, d l tai duoc tiln hanh nhim nghien cyu tinh khang khuIn cua san phlm Loxain tren Invitro. danh gia tac dung dilu tn bdng cua c h i p h l m Loxain tren md hinh gay bdng nhiet thuc nghiem d chuot cdng tring

II. D 6 I TU'gNG VA PHU'aNG PHAP

1. Ddi tu'O'ng

1.1., Thuoc va chiit lieu nghien cieu - Thudc nghien cyu' Loxain d dang dung dich 500ml chat long trong suot, mau dd cam ddng nhlt Nong do 1,6g dyac lieu/ml, duac Cdng ty Cd phIn san xult va thyong mai Nam Y Aurvini san xult, dgt tieu chuIn ca so Loxain dyac pha loang trong uung mdi la d l u CO,

- Thudc dung trong nghien cuu Sulfadiazin- bac (biet duoc Silvadene®) dang kem bdi 1%

san pham cua Cdng ty cd phIn Dyac Trung Lfong H u l (Medipharco)

1.2. Chung vi khuan mau quoc te Bon chung vi khuIn quic t l , Pseudomonas

aeruginosa (ATCC 27B5Z), Staphylococcus aureus (ATCC 25913), Escherichia coli fATCC 25922), Klebsiella pneumoniae{ATCCBAA- 1705) duac nhap, bao quan va nudi cly va nghien cyu tai Khoa Vi sinh, Banh vi§n HQ-u nghi VietDCfC

1.3. Dong vat nghien CLPU

Chudt cdng chung Wistar ca hai giong, khoe manh, can nang 285 ± 30g do Trung tam dong vat thi nghiem Dan Phyang - Ha Tay cung d p Ddng vat dyac nudi trong phdng thi nghiem 7 ngay trydc khi nghien cO'U va trong suit thai gian nghien ciru trong dilu kien phdng thi nghiem vdi d l y du thirc an va nude uing tai Bd mdn Dyac ly - Trydng Dai hoc Y Ha Ndi

2. Phwcng phap

2.1. Danh gia hoat tinh khang khuan cua Loxain tren invitro

' ChuIn bl thudc thCr

Pha loang bac 2 cac dung dich thy nghiem vao cac I n g tube (1, 2, 4, 8, 16, 32) bing dlu CO. Dung dich gdc cd dd dam dac cao nen ndng dd pha bang tu' 1/2 -1/32 duoc chon d l danh gia hoat tinh khang khuan

* Chuan bi huyin dich

ChiJng vi khuIn c i n thi> dyac nudi cly thuin, qua dem L l y 3 - 5 khuan lac hoa tan vao nydc mudi 0,9%, dieu chinh d l dat huyIn dich cd ndng dp 0.5 Mac Fariand (tuong duong 10^CFU/1ml)

- Trong vdng 15 phut sau, pha loang huyIn dich tr^n b l n g canh thang Muller-Hinton v6 triing (ddi vdi vi khuIn d i mpc) hoac canh thang Muller - Hinton cd 2,5-5 % mau ciru, d l dat ndng dd 5 x 10^ CFU/lm! Pha loang huyIn dich vdi dung dich chii'a vi khuan de cd

(3)

• TAP CHi NGHIEN CU'U Y HOC Loxain vdi cac nong do tir 0,025 - 0,4g duac

lieu/ml

- U cac dng tube d 37°C/18 - 24 gid Sau thd'i gian u I m tr§n, l l y dich d' mdi tube c l y vao thach mau. 0 cSc dla thach d 37°C/18-24 gid, cd hoac khdng cd CO2 tiiy thuoc vao chung vi khuIn can thy K i l m tra c^c dla thach mau xem sy mpc cua vi khuIn dat khi 6 dTa chu'ng, vi khuIn moo tdt va a t i t ca cac dTa VI khuan moo thuIn nhlt, khi dd xac dmh ndng do ire c h i tdi thilu.

Trong nghien cyu vdi mdi chung vi khuIn d l u pha loang 5 ndng dd' 1/2, 1/4, 1/8, 1/16 va 1/32 so vd'i dung dich g l c Mdi ning dd duoc thy 5 mSu vdi mdi chiJng vi khuan.

Nhan dmh k i t qua tim ndng dd d'c che tdi thilu,

2.2. Danh gia tac dur)g cua Loxain tren mo hinh gay bong thipc nghiem

Chudt dyac chia thanh 5 Id, mdi Id 13 con, - Ld 1 (chung sinh hoc) khdng gay ton thyang bdng.

- Ld 2 (md hinh). gay bdng tren da Bdi d l u CO 4 lin/ngay

- Ld 3 (chyng dyang); gay bdng tren da B61 sulfadiazin - bac 4 lin/ngay

- Ld 4 (Loxain lilu thlp) gay bdng tren da Bdi Loxain 4 lin/ngay

- Ld 5 (Loxain lilu cao) gay bdng tren da Bdi Loxain 6 lin/ngay

• Bdi thudc hoacdau co

Gay bdng , Do dien tich vet bdng

V

Do dien tich vet bdng, giai p h l u benh v l t bdng

2.3. Sa do nghien CLFU quy trinh gay bong nhiet

Chudt d cac Id duac gay ton thuang bdng tren da theo md hinh gay bdng nhiet b l n g dung cu kim loai theo md ta cua Durmus AS va cdng sy, Vu Thi Ngoc Thanh [6; 10]

' Cao long chuot va gay bong Cao Idng chudt tai vi tn ngang mao chau vd'i dien tich 2 ben la 6 x 6cm Vat gay bdng kim loai (nang 200g, dydng kinh 2,5 cm) duac nhung trong nude sdi 100°C cho tdi khi dat nhief dd h l n g dmh, dat vudng gdc len vi tri cao Idngchudt 35 giay va khdng dyoc tac ddng them lye tiy ben ngoai

' Cach thu'c boi thuoc

D l u CO, sulfadiazine - bac va Loxam dyac nhd 0,1 ml/1vlt bdng, sau do xoa d l u 5 lan/1 v l t bdng trong 15 giay, dam bao phu kin v l t bdng Khoang each giua cac lln bdi each nhau 2 gid.

2.4. Chi so nghien CU'U

' Ty Id c h i t cua chuot sau khi gay bdng Sau khi gay bdng, chudt dyac nudi trong cac chuong rieng biet cho an va udng nude hang ngay nhy nhau giu'a cac chudng. Dong thdi t i l n hanh quan sat, ghi lai ngay chit cua chudt va Id tyang irng (nlu co).

TCNCYH 107 (2)-2017

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TAP CHI NGHIEN CU'U Y HOC ' Chi s6 hinh thai dai t h i

Tinh trang ton thuang tai v l t bong sung, ndng, dd, phu n l quan sat blng mat thudng va ghi lai blng may anh ky thuSt sd. Vet bdng khdi la luc b l mat khd, mep v l t bdng tiln g i n nhau, quan sat thly khdng con hien tuang syng tay tren v l t bdng Do dien tich v l t bdng tai cac ngay 7, 14, 21 sau khi gay bdng Tinh phan tram phuc hoi ton thyang

each do ap gily trong Idn vung ton thyang, dting biit Idng ghi lai theo vien ton thuang, sau dd scan lai hinh anh dd, do dien tich blng phIn m i m ImageJ Basics ver 1 38 da duoc To chyc Y t l T h i gidi cdng nhan la phan m i m d l do dien tich cho cac nghien cifu y sinh hoc

• Chi sd hinh thai vt t h i

Tai thai dilm 21 ngay, IQc cac vet bdng da bong hit vay va dang hdi phuc hoac da khdi, chudt dyac gay me, l l y md benh hoc ngau nhien 3 chudt d mdi Id tai vi tri trung tam ton thuang Danh gia su tang sinh t l bao sai, tang sinh mach mau, tang sinh soi collagen, ty le bieu md hda vet thyang

Xiv ly so lieu: Sd lieu duac XLP ly theo thuat toan thing ke Microsoft Office Excel 2007 K i l m dinh s y khac biat cua 2 gia tn trung binh blng thuat toan x^ sy dung t-test Student, Su khac biet cd y nghTa thong ke, p < 0,05

III. K^T QUA

1. Danh gia tac dung cua Loxain tren In vitro

Loxain vdi ndng dd tir 0,025 - 0,4g dyac lieu/ml duoc thy tren 4 chung vi khuIn Qudc te la P aeruginosa, S aureus, E.coli, Kpneumoniae deu cho k i t qua vi khuan moc binh thydng, khdng co khac biet giu'a nhdm chyng va nhdm diing thudc thy Nen chung tdi chua xac dmh dyac ndng do ire c h i tdi thilu CLia Loxain

"> Tac dung cua Loxain tren mo hinh bong nhiet thLKC nghiem

Ty le chet cua cac id chuot Thai gian sau khi gay bdng ty le chudt chit dyac ghi lai theo bang sau"

Bang 1. Ty le chudt chet d- cac Id chuot sau gay bong

Ld Tyle chudt chit

Md hinh 2/13

Chirng du'cng 0/13

Loxain lieu thap 1/13

Loxain lieu cao 1/13

Theo ddi nghien cu'u cho thly chudt chit trong thai gian tii' ngay 4 den ngay 7 sau khi gay bdng, ban d l u nhan thay chudt giam van ddng, an it di d i n bd an va bd uIng nydc sau do tif vong, ty le chit cua Id bdi d l u co la cao nhlt (2/13), Loxain ca 2 lilu ed ty le chet nhy nhau (1/13), 10 bdi sulfadiazine - bae la thlp nhlt (0/13)

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- TAP CHi NGHIEN CU'U Y HOC 2.2. Dien bien dai the tai vet bong

Ngay sau khi diing nhiet de gay bdng: v l t bdng cd mau trIng nga, khdng phdng rdp, cd ranh gidi ro vdi viing da lanh. Khoang 1 - 2 gid sau, ria xung quanh v l t bdng nhin rd qulng sung huylt

Anh minh hoa chudt s6 13 sau khi gSy bdng

Anh 1. Da chuot ngay sau khi gay bdng Cac vet bong bdi dau co

- Sau 3 ngay, 100% cac vet bdng cd lost.

v l t bdng d trong tinh trgng hoai ty, tren b l mat cd nhilu 6 loet Cac v l t loet rdng dan, chilm khoang 50 - 55% dien tich b l mat v l t bdng, chu^a nhilu dich tiet m l u due Vting xung quanh vit bdng phii n l , nhung v l n cd ranh gidi vd'i vung da lanh

- Sau 7 ngay, da s i v l t loet v l n chay dich, mOt so v l t loet da khd va b i t d l u hinh thanh vay tilt. Viing da xung quanh v l t bdng v l n sung huylt

- Sau 13 - 14 ngay, t i t ca cac v l t bdng d l u da hinh thanh vay t i l t va 14/22 v l t bdng b i t d l u bong vay de Id vung ton thuang phia dydi dang phuc hdi, cac v l t bdng khd Viing da xung quanh ton thyang khdng cdn sung huyet

- Ngay thu' 21, tat ca cac v l t bdng da bong vay, 5/22 v l t bdng van cdn ydt, sd qdn lai da khd, vung da ton thuang thu hep

' Cac vdt bong boi sulfadiazin-bac 1 % , Loxain l i l u t h i p va Loxain lieu cao

Anh 2. Da chuot sau khi gay bdng 1 gid*

- Ngay thit' 14, cac v l t bdng bong vay tilt nhanh, v l t bdng khd, hinh thanh seo sdm, vung ton thyang cdn rIt nhd.

- Ngay thy 21, hau h i t cac v l t bdng hdi phuc, tao thanh seo nhd phang so vdi mat da

3. Wlu-c do thu hep dien tich bong Sau 7 ngay diing thudc, dien tich bdng khdng cd sy khac biet d t i t ca cac Id nghien CU'U Tir ngay thif 14 sau diing thuoc, di$n tich cac v l t bdng da b i t dau thu hep rd r§t, K i t qua dyac trinh bay trong bang 2

Loxain d ca 2 lieu cd tac dung lam thu hep dien tich bdng nhanh han id chung bdi d l u CO vao cac ngay 14 va 21 sau dung thulc, sy khac biet cd y nghia thing ke (p < 0,05) Mire do thu hep dien tich bdng d Id bdi Loxain so vdi Id bdi sulfadiazine - bac 1 % tyang duang nhau d h l u h i t cac thai d i l m (p > 0,05).

Loxain lilu t h l p va lilu cao cd tac dung lam thu hep dien tich v l t bdng tyang dyang nhau tai cac thdi diem 14 va 21 ngay (p >

0,05) bang 2

TCNCYH 107 (2)-2017

(6)

TAP CHI NGHIEN CU'U Y HOC Bang 2. PhIn tram thu hep dien tich v l t bong tren da chuot

L6

3 (chi>ng difang) 4 {loxain lilu Blip) 5 (loxatn lilu cao)

ThOT diem

N H

N„

N„

N j , N,.

Hi, N„

N2,

Thu hep dietLtich v l t bong (%) X ± SD

79,24 ±8,95 87,36 ±2,83 87,12 ±5,24 95,84 ± 1,79 88,90 ±5,08 94,20 ±2,61 89,19 ±5,45 94,33 ± 3,33

P3.3 < 0,05 P3.2<0,05 P4.2 < 0,05 P4-2 < 0,05 Ps.2<0,05 P5.!<0,05

P

p „ > 0 , 0 5 p<.3>0,05 P5-3>0,05 P5-3>0,05

P5-4 > 0,05 P5.<>0,05

4. Giai phlu benh vi the da tai vet bdng

, C l u triic vi t h i da chudt tai vi tri ton thuang bdng duac t i l n hanh tai thai d i l m 21 ngay sau gay bdng, mdi Id lly nglu nhien 3 chudt, ket qua duac tdm t i t nhy sau

Bang 3. Giai phiu benh da chudt sau 21 ngay

L6 Ma chudt Ket qua

^, , . , ^ „ ^ ^ Da chuot binh thuong Cac ap thuang bi. trung bi, ha bi

Chirng sinh hoc 1,2,3 . ^ a . a - -

nguyen ven

Thyang bi tdn thyang nhilu, b i t d l u cd hi^n tyang tang sinh D l u CO 15, 2 1 , 22 xa va cac t l chirc xung quanh. Viem va xung huyet myc 66

vya lap dudi thyang bi

- . . Thyang bi ton thyang it, da cd hien tyang tang sinh xa va cd 25, 26, 33 hien tyang liln seo, v l n cdn hi^n tyang xung huyet d' vung

Idpdudi thuang bi

Thyang bi ton thyang it, da cd hien tuong tang sinh xa manh Loxain lilu thlp 37, 44, 45 va liln seo, v i n con hien tyang xung huyet d' viing Id-p dydi

thuang bi

Thyang bi ton thyang it, da co hien tyang tang sinh xa manh Loxain lilu cao 50, 53, 56 va cd hien tyang lien seo, van cdn hien tyang xung huylt a

vung Idp dud^i thuang bi 1%

(7)

• TJC^P CHI NGHiEN CUU Y HOC

2 , ' - - ^ r . ' • " •

Anh 3. Chuot s o . l (chu'ng sinh hoc) (HEX 10) Da chudt binh thyang 1: TuySn bS, tuySn tiSt md hoi 2 L&p bi4u bi bl tdn thimng 3: ChSn bi

Anh 4. Chuot so 22 (boi dau co) (HE x 100) 1 Tdn thwong dang bong nwac 2. BiSu bi Ton thuang bdng dang bong nude, cac td chyc dang b i t d l u dyac tai tao mdr cac t l bao lympho, tyang bao xen lln tang sinh cac to chyc hat va mao mach

•rr'r

1

Anh 5. Chuot so 25 (boi sulfadiazine - bac 1 % ) ( H E x 1 0 0 )

1 Xung huySt; 2. Chan bi

Cdn ton thyang nhe, cac td chyc da duoc tai tao mdi.

Anh 6. Chuot so 37 (boi Loxain lieu thap) (HEX 400)

1 Xung huySt, 2 Bong nimc; 3: BiSu bi;

4- T4 bao viem

Ton thuang bdng cdn it, bdng nydc nhd hinh thanh, cac to chyc da dygc tai tao mdi tang sinh cac to chyc hat va tan mach

3

Anh 7. Chuot s6 53 (boi Loxain l i l u cao) (HE x 10) 1' Seo hinh thanh; 2-Vung khongcdtuySn dmifida. 3 TuySn dwoi da. 4 Bl4u bi.

Da chudt da hinh thanh seo.

TCNCYH 107 (2)-2017

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TAP CHi NGHIEN CU'U Y HOC ' Cd sy khac biet ro v l c l u triic hinh thai vi the cua da vung bdng giQ'a Id bdi d l u co va cac Id

bdi thuoc,

- Tai v l t bdng bdi dau co. viing v l t bong bilu bi che phii it Chya thly cd hien tyang tang sinh t l bao Idp day cung nhu chua thly cd hien tyang tang sinh xa d- Id-p dydi thyg-ng bi nhyng da cd hien tuang xam nhap cua cac te bao thyc bao va cac lympho bao.

- Tai v l t bdng bdi thudc viing v l t bdng bieu bi che phu rdng, cdn it ton thyang Cd hien tugng tang sinh t l bao Idp day va cac td chyc xa 6' Idp dydi thuang bi Mot sd chuot da cd hi$n tuang hinh Ihanh seo rd ret (viing da khdng cd td chyc tuyin dydi da) Tuy nhien, v l n cdn hien tyong sung huylt d mot so v l t bdng

IV. B A N L U A N

Loxain la san pham da ty lau dygc diing cho cac trudng hap bdng do napan trong chiln tranh va vet thuong do nguyen nhan khac nhy zona, v l t thyang hd, . d l u cho k i t qua liln da nhanh, an toan va dyac ngudi benh danh gia cao, muc dich ciJa nghien nay nhim chirng minh hi$u qua va tinh an toan nhlm phat tnen Loxain trd thanh thudc chu'a bdng.Thanh phan chu y l u la curcumin va g- caroten dyac chilt xult tir cu nghe va tinh dlu g l c - hai nguyen lieu rat pho biln d nydc ta Da cd nhtfng nghien cii'u khoa hoc chyng mmh tac dung curcumin va p - caroten tren v l t thuang ndi chung va v l t bdng ndi rieng, cung nhu vai trd tang cudng kha nang mien dich[81 Curcumin la thanh phIn chu y l u cua cu nghe, mot bai cu rlt pho biln d nud-c ta. Cu ngne duoc biet den ty lau nhy mot loai cu cd tac dung nhanh lien seo, riit ngln thdi gian liln v l t thuang va dygc sy dung rdng rai

P - caroten la mot trong ba tien chat ciia"

vitamin A, cd nhilu trong cac loai cu cd mau nhy, glc, ca rdt hoac rau xanh Vitamin A cd vai trd quan trong khdng the thilu cho hoat ddng cua mot s i ca quan trong ca the mit, da va to chii'c da, he thing miln dich

Da cd nhieu nghien cyu trong nydc va tren

t h i gidi tim h i l u va chifng mmh tac dung cua curcumin va p - caroten trong Y hoc [8].

Dya vao cac ca sd khoa hoc nhy tren, chiing tdi chon Loxain lam nguyen lieu nghiSn cyu tran md hinh gay bdng nhiet 6 chuot c6ng chung Wistar n h l m tim ra loai thudc dtlu trj tai cho v l t thuang bdng dyac san xuat tii' nhOng nguyen lieu cd s i n trong nude nham thay thi cho nhCpng thudc nhap ngoai dat tien hien nay

Nghien cyu tac dung khang khuIn cua Loxain duac t i l n hanh tai Khoa Vi sinh - Benti vien HCJ-u nghj Viet Dye do tai ca sd nay co day du trang thilt bi c l n . t h i l t nhy: chung vi khuan m l u quIc t l , dung cu nudi cay, can bd tham gia nghien cu'u la nhu'ng ngydi cd kinh nghiem Sau khi nudi c l y va tim dyac ndng dd ifc c h i tdi thilu len 4 chung vi khuIn cua Loxain tren invitro thi se l l y m l u b^nh pham

"tren v l t thyang bdng d l nudi cay va danh gia tac dung khang khuIn cua Loxain

Vdi mdi Chung vi khuan d l u pha loang 5 ndng dd 1/2, 1/4, 1/8, 1/16, 1/32 so vdi dung dich gdc, vdi moi mot ndng dd duac hoa vdi Loxain tygng ifng vm cac nong do 0,025 - 0,4g dygc heu/ml K i t qua cho thly tat ca cac nong dd pha loang nhy trgn chya tim duac ndng do Loxain toi thieu O'c e h l duac cac

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• TAP CHI NGHIEN CU'U Y HOC chung vi khuan tren Do do chiing tdi khdng

t i l n hanh lay m l u benh pham tren v l t thuang d l nudi cay va danh gia tac dung khang khuln.

D l i tuang nghien cii'u la chudt eong se d l dang tao ra tinh trang v l t thuang vol cac tieu chuIn cua loai, kich thydc, dd sau v l t thuang mot each phCj hap [10] Chudt cdng la loai cd sifc chiu dung cao, sire d l khang tdt r l t phu hap trong viec gay md hinh v l t thuong da Ben canh dd, chudt cdng trIng la loai ddng vat phd biln, phii hap vdi d i l u kien cCia nhilu phdng thi nghiem, do vay chung tdi da lua chon chudt cdng trlng d l gay md hinh bdng.

Bdng do rat nhilu nguyen nhan gay ra nhu nhiet, hoa chit, dien, bye xa nhiet Trong do bdng do nhiet la nguyen nhan hay gap nhlt 84 - 94% Da cd nhieu md hinh gay bdng nhiet duac xay dyng va thuc hien bdi cac tac gia trong nude va nydc ngoai sy dung thd lam ddng vat thyc nghiem [6, 11]

Trong nghien ciru nay, chiing tdi da gay bdng thy nghiem tr§n chudt vdi dung cu kim loai ed nhiet dd lOO'C, trong cac khoang thai gian 35 giay d l gay d y a c ton thyang bdng phii hap (tuang yng ton thyang bdng dd III)

Ton thyang bdng gay nen phan u'ng viem tai ehd, tiep dd tinh trang nhilm khuan v l t bdng da lam anh hydng den tinh trang toan than Chinh vi vay, sau khi bi bdng, chudt a trang thai met, it hoat ddng, thydng n l m yen Tinh trang an uong kem, cdng vd'i su mat nydc. m I t protein qua v l t bdng lam chudt bi suy kiet, kem theo dd la sy nhilm khuIn tai v l t bdng cd t h i lam chudt bi tu vong [4]

Nghien ciru cho thay chudt c h i t trong khoang tii' ngay 4 d i n ngay 7 sau khi gay bdng K i t qua nay phii hap vdi khoang thdi

gian hay gay tCr vong n h l t cua bdng (giai doan nhilm triing, nhilm doe t y ngay 4 d i n ngay 20)

K i t qua cho thly, Id bdi sulfadiazine -bac khdng bi t y vong do sulfadiazine -bac cd tinh khang khuan lam giam qua trinh nhilm khuan v l t bdng Ca 3 Id bdi ta dyac va Loxain d l u ed chudt bi ti> vong, tuy nhien 2 Id bdi Loxain lilu thap va lilu cao cd ty le c h i t cao han so vdi Id chu'ng duang (Bang 1) Loxain lam giam so Chudt chit so vdi Id md hinh (bdi d l u co) CO t h i do san p h l m nay ed tac dung tao ra hang rao bao ve ehdng su xam nhap cua vi khuan vao vet bdng hoac Loxain cd tac dung khang khuan true tilp tren v l t bdng. Mac dii tren Invitro, Loxain vdi ndng do kha cao (0,4g ayac lieu/ml) khdng cho thly kha nang khang khuan tren 4 chiing vi khuIn qudc t l thydng gap, d i l u nay cd the do vi khuan thuc t l tren vet bdng va m l u vi khuIn quoc te co t h i cd sy khac biet v l chung va kha nang nhay cam vdt Loxain Dk khlng dmh ve su lien quan giya ty le c h i t va tinh khang khuan cua Loxain tren v l t bdng thi can nghien ciru vdi ed m l u idn han, dong thai tien hanh lay mau vi khuIn tryc tiep tren v l t thyang bdng d cac giai doan khac nhau, sau dd nudi cly, dinh danh va danh gia kha nang khang khuan ciia Loxain tren cac chiing vi khuIn nay

O Id chudt bdi dau co, nhyng ngay d l u sau bdng t i t ea cac v l t bdng d l u cd loet. cac v l t loet rdng d i n chay nhilu dich tilt va cd miii khd chiu, nhu'ng ngay sau cac v l t loet kho dan, thu hep dien tich ton thuang, tuy nhien d i n khi k i t thiic nghien cyu g Id nay v l n cdn mdt sd v l t bdng cdn chay dich tilt Tai chd v l t bdng duae bdi d l u co khdng co tac dung khang khuan, ehdng viem chinh vi vay lam cho phan u'ng viem eang manh va keo dai

TCNCYH 107 (2)-2017

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TAP CHi NGHIEN CUU Y HOC • c0ng vdi tinh trang nhiem khuan lam v l t thuang (au liln Qua trinh tai tao hdi phuc v l t thuang ca tren dai the va vi the d l u tien then r l t Cham, k i t qua nay phCi hap vdi nghien ciru cua mdt nghien ciru duge t i l n hanh trudc day [6]

O 2 Id bdi Loxam, thdi gian lien v l t thyang bdng tyang t y nhy Id bdi sulfadiazine - bac, sau 7 ngay cac v l t bdng khd va b i t dau hinh thanh vay tilt d i n ngay thu- 21 da s i cac v l t bdng da tao seo. Myc dd thu hep dien tich v l t bdng nhanh han so vdi Id md hinh (p < 0,05) va tuang t y nhy Id chu'ng duang (p > 0,05) TCr k i t qua tren cho t h l y Loxain cd tac dyng d i l u tri tgi ehd v l t thyang bdng tyang tu sulfadiazine - bac Tren hinh anh vi t h i v l t bdng cung co s y tang sinh xa manh.

cd the do Loxain cd tac dung kich thich tang sinh xa t3i n p t i n thuang Phan tich k i t qua cho t h l y myc do thu hep dien tich v l t bdng d 2 Id bdi Loxain lieu thap va lilu cao la khdng cd su khac biet. T u k i t qua nghien c y u s u khac biet v l tinh trang toan than, tac dung tiln v l t thuang bdng ciia 2 lilu Loxain t h l p va cao khdng cd khac biet rd ret, chiing tdi kiln nghi su' dung Loxain lilu t h l p vl sd l l n bdi thudc trong ngay (a 4 l l n se d l ap dung tren thyc te

V. K^T LUAN

Ty k i t qua nghien cu'u v l tinh khang"

khuan va tac dung dilu tn tai cho vet thyang do bdng nhiet ciia Loxain tren chudt cdng trlng, k i t qua cho thay

- Vdi cac ndng dd Loxain tie 0,025 - 0,4g/

ml chua xac dmh ndng dd tdi thilu L>C e h l 4 chiing vi khuan la; P aeruginosa. S.aureus.

Ecoli va K pneumoniae tren Invitro

- Loxain cd tac dyng dieu tn tai chd vlt thuang bdng nhiet thye nghiem tren chuot cdng trang the hien a thdi gian liln khdi vlt thyang bdng d i l n ra nhanh, tang toe do thu hep v l t thuang bdng Hieu qua dilu tn vlt thyang bdng ciia Loxain bdi 4 lin/ngay va 6 Iln/ngay la tyang dyang nhau

LOT cam e n

Nhdm nghien c y u tran trong cam an Cdng ty Co phIn San x u l t va Thuong mai Nam Y Aurvini da tai tra eho ehiing tdi thyc hien de tai

TAI LIEU THAM K H A O 1. Le The Trung (1997) Nhyng dilu cIn biet v l bdng. NhaxuBtban Y hoc, H^ Noi

2. Le T h i Trung (1997) Bdng - NhCi'ng kiln thicc chuyen nganh. Nha xudt ban Y hoc, Ha NOI.

3. N g u y i n Gia T i l n , Pham Gia Khanh, Pham Dinh Bang(1997),Tac dung dilu tn tgi chd v l t bdng do nhi§t blng thudc mff Maduxin Tap chi Y hoc thuc hanh, 11 (342), 36-41

4. Le The Trung, Tran Xuan Van, Nguyin Liem, N g u y i n Dinh Bang, Dao Xuan Vinh (1991) Nghien ciru thudc Maduxin oil dieu tn tai chd nhiem khuIn mu xanh v l t bdng, Tap chi Y hoc thwc hanh. 5, 23 -26.

5. Pham Phan Djch, N g u y i n Van Ngoc (1986) Anh hydng cua mat ong d i n su tai tao hdi phuc v l t bdng da chudt cong trlng Tap chi Y hoc Viet Nam (chuyen d§ hinh thai hoc), 2 , 4 3 - 4 7 .

6. Vu Thj Ngoc Thanh, Le Van Phiing, L§

Huy Chinh, Hoang Tich Huy§n (2001) Nghien cii'u tinh khang khuan ciia chitosan tren bdng nhiet thuc nghiem. Tap chi Duvc hoc, 229, 19

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— ~ ^ ^ ^ — ^ - ^ ^ ^ ^ ^ - . ^ — TAP CHi NGHIEN CCPU Y HQC

7. Pham Toan Thang (1993) Thudc Sil- 10. Wanda A. Dorsett-Martin, Annette B.

vadence cream 1 % (Silver sulfadiazin 1%), Wysocki (2008) Rat Models of Skin Wound Thong tin bong, 3, 1 5 - 1 7 Healing, Sourcebook of Models for Biomedical

8. Bo mdn Du-ac ly (2011) Trydng dai Researc/7, 6, 6631 -6638

hoc Y Ha Ndi, Diyac/y rtoc fap 2, /V/7a xu^f 11. Durmus AS, Han MC, Yaman I ban giao due. Ha Noi, 203 - 213. (2009) Comperative evaluation of collagenase 9. Mehrabani et al (2015) The Healing ^^^ silver sulfadiazine on burned wound heal- Effect of Curcumin on Burn Wounds in Rat, 1^9 ' " rats, Firat Universitesi Saglik Biiimleri World J Plast Surg, 4(1), 29-35 ~ Veteriner Dergisi,23, 135-139

Summary

STUDY ON ANTIBACTERIAL ACTIVITY /W VITRO AND HEALING EFFECT ON BURN WOUND IN RAT OF LOXAIN

Loxam was used to investigate the antibacterial activity in In vitro and healing effect on heat burn wounds in rat Antibactenal activity of Loxain was evaluated in 4 international bacteria strains Pseudomonas aeruginosa. Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae in In vitro in burn wound model in rat, Wistar rats were divided in to 5 groups, group 1 was served as control, similar burn ulcers were produced on antenor surface of thigh of 50 rats in groups 2 to 5, Then group 2 served as control was treated with palm oil 4 times per day, group 3 served as positive control were treated with silver sulfadiazine ointment, group 4 and 5 were treated with Loxain ointment 4 and 6 times per day in 21 consecutive days The result showed that In vitro study, the concentration of Loxain from 0 025 g/ml to 0 4g/ml do not have antibactenal activity against 4 tested bacteria strains In vivo study, groups treated with Loxain oitment achieved reduced healing time, wound healing effect in 2 groups treated with Loxain ointment 4 and 6 times per day were the same as in 21 consecutive days

Keyword: Loxain, antibacterial activity, Wistar rat, heat burn wound, healing effect

TCNCYH 107 (2)-2017

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