Analiza interakcija laktobacila sa crevnom mukozom pacova
Analysis of interactions of lactobacilli with rat gut mucosa
Докторанд
Lukić, Jovanka M.Ментор
Jovčić, BrankoЧланови комисије
Begović, JelenaStrahinić, Ivana
Milenković, Marina
Kojić, Milan
Метаподаци
Приказ свих података о дисертацијиСажетак
Probiotici predstavljaju žive mikroorganizme koji, nakon unošenja u gastrointestinalni
(GI) trakt, ostvaruju pozitivne efekte na zdravlje domaćina. Reakcija domaćina na unos
probiotika u velikoj meri zavisi od sposobnosti bliske interakcije bakterija sa epitelnim
ćelijama GI mukoze. S druge strane, s obzirom na nepoznatu antigenu prirodu unetih
bakterija, kod imunokompromitovanog domaćina je prisutan rizik od imunske reakcije
crevnog tkiva što može da dovede do narušavanja integriteta mukozne barijere i hronične
inflamacije u GI traktu.
Cilj istraživanja bio je ispitivanje efekta soja Lactobacillus fermentum BGHI14,
alohtonog za GI trakt pacova, nakon peroralnog unosa u zdrave pacove i u pacove sa
kolitisom indukovanim TNBS-om (trinitrobenzensulfonat). Metodološki, u eksperimentima
su praćeni: telesna masa pacova i ekspresija iRNK za parametre inflamacije (IL-1β, TNFα,
IL-17F), pokazatelje ćelijskog stresa (HSP70) i parametre uključene u održavanje
integriteta mukoze (TJP1); zatim su r...ađene histološke i biohemijske analize i analiza
sastava crevne mikroflore. Rezultati istraživanja su pokazali imunostimulišuće delovanje
soja BGHI14 na nivou tkiva kolona nakon unosa u GI trakt zdravih pacova u prvih 16 dana
peroralnog tretmana pacova. Iako se, histološki, sa produžetkom tretmana pacova sojem
BGHI14 tokom narednih 12 dana, imunska reakcija u tkivu kolona povukla, nivoi iRNK za
proinflamatorne IL-1β i TNFα citokine ostali su povišeni što ukazuje na rizik od
nekontrolisane inflamacije u slučaju naknadnog oštećenja epitelne barijere kolona.
U istraživanju je pokazano da je nakon imunostimulacije tkiva kolona sojem BGHI14,
u slučaju indukcije kolitisa, ali uz nastavak tretmana sojem BGHI14 došlo do indukcije
transkripcije iRNK za HSP70 protein, kako u ranoj (48 h) tako i u kasnoj (7 dana) akutnoj
fazi kolitisa. Povećanje transkripcije Hsp70 gena, sudeći po histološkim i inflamatornim
pokazateljima, kao i promenama telesnih masa pacova tokom eksperimenta, nije bilo
praćeno pozitivnim delovanjem soja. S druge strane, prestanak tretmana sojem BGHI14
nakon indukcije kolitisa doveo je do manje izraženog pada telesnih masa životinja u poređenju sa kontrolnim pacovima sa kolitisom, iako bez pratećeg smanjenja inflamatorne
reakcije u tkivu kolona, bar u kasnoj akutnoj fazi bolesti (sedam dana od indukcije)...
Probiotics are life microorganisms that, after administration in gastrointestinal (GI)
tract, excert positive effects on host’s health. Host reaction to probiotic administration
largely depands on ability of bacteria to closely interact with epithelial cells of GI mucosa.
On the other hand, considering the unknown antigenic nature of administered bacteria, in
immune-compromised host there is a risk of immune reaction of gut tissue which could
lead to disturbance of mucosal barrier integrity and chronic inflammation in GI tract.
The aim of the study was to examine the effects of the strain Lactobacillus fermentum
BGHI14, which is alochtonous to GI tract of rats, after peroral administration in healthy
rats and in rats with TNBS (trinitrobenzenesulfonate)-induced colitis. Methodologically,
following parameters were examined in experiments: body masses of rats and expression of
mRNA of inflammatory cytokines (IL-1β, TNFα, IL-17F), as well as markers of cellular
stress (HSP70) and barrier ...integrity maintenanace (TJP1); next histological and
biochemical analyses and microflora profiling were performed. Results of the study
indicated immune-stimulating effects of BGHI14 in colon tissue after administration in GI
tract of healthy rats in first 16 days of peroral treatment of rats. Although, histologically,
with prolongation of BGHI14 treatment of rats for next 12 days, immune reaction in colon
tissue had retreated, mRNA levels of proinflammatory IL-1β and TNFα cytokines remained
elevated which points to the risk of uncontrolled inflammation in the case of subsequent
colon epithelial barrier damage.
In research it was shown that after immunostimulation of colon tissue with BGHI14, in
the case of colitis induction, but with sequel of treatment with bacteria, transcription of
Hsp70 gene was induced, in early (48 h) as well as late (7 days) acute phase of colitis. The
increase of Hsp70 gene transcription, according to histological and inflammatory markers,
as well as body mass changes during the experiment, was not followed by positive action of
the strain. On the other hand, the cessation of treatment with BGHI14 after colitis induction
had led to less pronounced body mass decrease compared to control colitic rats, but without concomitant reduction in inflammatory scores in colon tissue, at least in late acute phase of
disease (seven days from induction)...