Altered expressions of endothelial junction protein of placental capillaries in premature infants with intraventricular hemorrhage

Latar belakang: Hipoksia plasenta menimbulkan stres oksidatif yang merusak protein penaut kapiler. Penelitian ini bertujuan mengevaluasi perubahan ekspresi protein penaut endotel pada kondisi hipoksia dan melihat kaitannya dengan kejadian perdarahan intraventrikel. Metode: Penelitian ini menggunakan plasenta bayi prematur (29 hipoksia dan 29 non hipoksia) sebagai model penilaian integritas vaskuler. Kadar hypoxia inducible factor (HIF)-1α diukur sebagai respons jaringan plasenta terhadap hipoksia, sedangkan malondialdehide (MDA) dan glutathion (GSH) diukur sebagai petanda stres oksidatif. Ekspresi protein penaut endotel (N-kaderin dan okludin) dinilai dengan imunohistokimia. Perdarahan intraventrikel dianalisis dengan ultrasonografi kepala pada hari ketiga. Uji t tidak berpasangan, uji Mann-Whitney dan uji kai kuadrat digunakan untuk menganalisis data secara statistik. Hasil: Kadar HIF-1α dan MDA lebih tinggi {13,64±8,70 pg/ mg protein dan 10,31 pg/mg protein (rentang 1,92–93,61)} pada kelompok hipoksia dibandingkan kelompok non-hipoksia {10,65±5,35 pg/mg protein and 9,77 pmol/mg tissue (rentang 2,42–93,31)}. Kadar GSH identik pada kedua kelompok {38,14 (9,44–118,91) dan 38,47 (16,49–126,76) ng/mg protein (p=0,810). mRNA N-kaderin (0,13) dan okludin (0,096) lebih rendah pada kelompok hipoksia dibanding non-hipoksia (p=0,001). Ekspresi protein N-kaderin (3,4; 75,9; 6,9; 13,8 0%) dan okludin (20,7; 3,4; 69,0; 3,4; 6,9%) pada kelompok hipoksia tidak berhubungan dengan perdarahan intraventrikel (p=0,783 dan p=0,743). Background: Placental hypoxia may lead to oxidative stress, which inflicts damage to capillary protein junction. The aim of this study was to evaluate altered expression of endothelial junction protein of capillaries in hypoxia condition and to observe its correlation with the incidence of intraventricular hemorrhage in premature infants. Methods: A cross-sectional study was conducted by using placental tissues of premature infants as amodel of capillary integrity (29 hypoxic and 29 non-hypoxic). Hypoxia inducible factor (HIF)-1α was measured to define placental tissue response to hypoxia; malondialdehyde (MDA) and glutathione (GSH) served as markers of oxidative stress. The expressions of junctional proteins, N-cadherin and occludin were analyzed by immunohistochemistry. Intraventricular hemorrhage (IVH) was detected by cranial ultrasound at the third day. Unpaired t test, Mann-Whitney, and Chi-square tests were used to analyze the data. Results: The HIF-1α and MDA levels were slightly, but not significantly, higher in hypoxia group {13.64±8.70 pg/mg protein and 10.31 pmol/mg tissue (ranged 1.92–93.61), respectively} compared to non- hypoxia group {10.65±5.35 pg/mg protein and 9.77 pmol/mg tissue (ranged 2.42–93.31)}. GSH levels were not different in both groups (38.14 (ranged 9.44–118.91) and 38.47(ranged 16.49–126.76) ng/mg protein, respectively. mRNA expression of N-cadherin (0.13) and occludin (0.096) were significantly lower in hypoxia comparedto non-hypoxia group (p=0,001), while protein expression of N-cadherin (3.4; 75.9; 6.9; 13.8%) and occludin (20.7; 3.4; 69.0; 3.4; 6.9%) in hypoxia group was not associated with IVH (p=0.783 and p=0.743). Conclusion: Hypoxia altered expression of endothelial junction protein in placental capillaries, but no association with intraventricular hemorrhage was observed.