Extracellular miR-17, miR-29a, miR-181a, proinflamatory cytokines and oxidative damage parameters levels in blood of patients with gestational diabetes mellitus and gestational arthierial hypertension

[M. Z. Toljić]

85 str. [5] listova

Biologija - Genetika / Biology - Genetics

Gestacijski dijabetes melitus (GDM) i gestacijska hipertenzija (GH) predstavljaju neke od najčešćih komplikacija koje se mogu javiti u trudnoći, a poznavanje mehanizama koji leže u njihovoj osnovi ključni su za razvoj adekvatnih mera prevencije i lečenja. U prikazanoj studiji ispitivan je nivo odabranih mikroRNK (miR-17, miR-29a i miR-181a), genske ekspresije citokina (IL-1β, TNF-α, IL-6 i IL-17) i parametara oksidativnog stresa (reaktivne supstance tiobarbituratne kiseline – TBARs, i 8-hidroksi-2’-deoksiguanozina – 8-OHdG) u perifernoj krvi trudnica sa GDM-om, GH-om, kao i zdravih trudnica. Kod GDM trudnica utvrđen je značajno niži nivo ekspresije miR-29a i značajno viši nivo ekspresije IL-1β u poređenju sa kontrolom. Oba parametra imaju dovoljan dijagnostički potencijal za diskriminaciju trudnica sa GDM-om, a njihovo kombinovano korišćenje ima veći dijagnostički potencijal. U GH grupi utvrđen je značajno viši nivo ekspresije TNF-α u odnosu na kontrolnu grupu. Ipak, ovaj parametar nije pokazao potencijal korišćenja kao biomarker gestacijske hipertenzije. Dobijeni rezultati ukazuju na povišen nivo lipidne peroksidacije u obe ispitivane grupe, dok je u GDM grupi pokazan i značajno viši nivo DNK oštećenja nego u kontrolnoj grupi trudnica. In vitro ispitivanjima utvrđeno je da Metildopa ne utiče značajno na nivo ispitivanih parametara lipidne peroksidacije i oštećenja DNK, te je isključen njegov mogući efekat na meren nivo parametara oksidativnog stresa hipertenzivnih trudnica. Promene nivoa genske ekspresije citokina i oksidativni stres uključeni su u patogenezu GDM-a i GH-a, dok u slučaju GDM-a dolazi i do promene nivoa ekspresije miRNK. miR-29a i IL-1β mogu se koristiti kao biomarkeri gestacijskog dijabetesa, dok se TBARs može koristiti kao biomarker oba patološka stanja.

Gestational diabetes mellitus (GDM) and gestational hypertension (GH) present some of the most common pregnancy-related complications. Understanding the mechanisms underlying their development is critical for appropriate prevention and management. In the presented study, levels of selected microRNAs (miR-17, miR-29a, miR-181a), cytokines gene expression (IL-1β, TNF-α, IL-6, IL-17) and oxidative stress parameters (thiobarbituric acid reactive substances – TBARs, 8-hydroxy-2’-deoxyguanosine – 8-OHdG) were measured in peripheral blood samples of pregnant women with GDM or GH, and healthy pregnant women. In GDM women significantly lower miR-29a and significantly higher IL-1β expression levels were found in comparison to controls. Both parameters had sufficient diagnostic potential to discriminate between controls and GDM, while the combined use of miR-29a and IL-1β showed better diagnostic potential. GH women had significantly higher TNF-α expression level than controls, although it does not appear to possess the potential to be used as biomarker of GH. Obtained results showed increased lipid peroxidation levels in both examined groups, while significantly higher DNA damage level was found in GDM group compared to controls. As it was shown by in vitro examinations, Metildopa did not have significant effect on lipid peroxidation and DNA damage parameters level. Therefore, we could assume that Metildopa did not influence measured oxidative stress parameters levels in GH women. Cytokines gene expression levels changes and oxidative stress are involved in GDM and GH pathogenesis, while GDM also involves miRNAs expression levels changes. miR-29a and IL-1β can be used as biomarkers of GDM, while TBARs can be used as biomarker for both pathological conditions.

gestacijski dijabetes melitus, gestacijska hipertenzija, miRNK, miR-29a, citokin, IL-1β, TNF-α, oksidativni stres, malondialdehid, 8-hidroksi-2’-deoksiguanozin

gestational diabetes mellitus, gestational hypertension, miRNA, miR-29a, cytokine, IL-1β, TNF-α, oxidative stress, malondialdehyde, 8-hydroxy-2’-deoxyguanosine

577.2:618.3(043.3)

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