Sri Nurbowo Ardi
Doctoral Program in Medical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia

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Intermittent hypobaric hypoxia induces oxidative stress and vascular remodeling in rat pulmonary arteries Sri Nurbowo Ardi; Muhammad Arza Putra; Dewi Sukmawati; Puspita Eka Wuyung; Wawan Mulyawan; Wardaya; Wiwien Heru Wiyono
Jurnal Medik Veteriner Vol. 9 No. 1 (2026): April
Publisher : Universitas Airlangga

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20473/jmv.vol9.iss1.2026.29-40

Abstract

Flight crews frequently experience intermittent hypobaric hypoxia (IHH), which may trigger oxidative stress and vascular remodeling in the pulmonary arteries. This study investigated the effects of IHH exposure on oxidative stress markers, tunica media thickness, and the expression of LR11 and HIF-1α proteins in rat pulmonary arteries using five groups of healthy male Sprague–Dawley rats (n = 5 per group). Twenty-five male Sprague–Dawley rats were divided into five groups: a control group and four treatment groups exposed to simulated altitudes of 25,000 ft (7,620 m) for 5 minutes per day over 1, 3, 7, or 14 days. Levels of HIF-1α and LR11 were measured using ELISA, oxidative stress markers such as γ-glutamyl-cysteinyl-glycine (GSH) and malondialdehyde (MDA) were analyzed spectrophotometrically, and tunica media thickness was assessed histologically. HIF-1α levels peaked after acute hypoxia exposure and declined with prolonged exposure, whereas LR11 levels progressively increased, peaking in the 14-day group. MDA levels, reflecting oxidative stress, were highest after 3 days of exposure, while GSH levels decreased in all hypoxia groups compared with the control. Histological analysis showed the greatest tunica media thickness in the 3-day exposure group, followed by gradual reductions. Although no statistically significant correlations were found between protein levels and tunica media thickness, similar directional trends suggest biologically relevant associations. Intermittent hypobaric hypoxia (IHH) induces dynamic changes in oxidative stress and vascular remodeling in rat pulmonary arteries. Acute hypoxia increases HIF-1α expression and oxidative stress, whereas repeated exposures appear to trigger compensatory adaptations, including LR11 upregulation and tunica media remodeling. These findings demonstrate measurable molecular and structural alterations underlying pulmonary vascular responses to repeated high-altitude exposure.
Analisis Biomarker Oksidatif dan Saturasi Oksigen Paru pada Tikus Hipoksia Hipobarik Intermiten Sri Nurbowo Ardi; Wiwien Heru Wiyono; Muhammad Arza Putra; Dewi Sukmawati; Puspita Eka Wuyung; Wawan Mulyawan; Wardaya Wardaya
Bahasa Indonesia Vol 25 No 2 (2026): Damianus Journal of Medicine
Publisher : Atma Jaya Catholic University of Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.25170/djm.v25i2.7093

Abstract

Pendahuluan: Hipoksia hipobarik intermiten (IHH) dapat mengganggu homeostasis redoks dan menurunkan saturasi oksigen. Malondialdehid (MDA) mencerminkan peroksidasi lipid, sedangkan reduced glutathione (GSH) menggambarkan kapasitas antioksidan endogen. Penelitian ini mengevaluasi MDA dan GSH plasma serta saturasi oksigen perifer (SpO₂) setelah paparan IHH akut dan berulang pada tikus. Metode: Sebanyak 25 tikus jantan Sprague-Dawley dibagi acak ke dalam lima kelompok (n=5/kelompok): kontrol normobarik dan IHH 1×, 3×, 7×, atau 14×. IHH diberikan sekali sehari dalam ruang hipobarik setara 25.000 kaki (7.620 m) selama 5 menit. MDA plasma diukur dengan TBARS dan GSH dengan uji DTNB. SpO₂ dicatat segera setelah paparan menggunakan pulse oximetry untuk rodensia. Perbedaan antarkelompok dianalisis dengan ANOVA satu arah dan Tukey HSD. Hasil: GSH berbeda bermakna antarkelompok (F=30,022; p<0,001) dan lebih rendah pada seluruh kelompok IHH dibanding kontrol, dengan nilai terendah setelah 7 kali paparan. MDA juga berbeda bermakna (F=14,481; p<0,001), dengan nilai tertinggi setelah 3 kali paparan; IHH 3× lebih tinggi daripada kontrol (p<0,001) dan IHH 14× (p=0,007). SpO₂ lebih rendah pada seluruh kelompok IHH dibanding kontrol (p<0,001), dengan rerata terendah setelah 3 kali paparan (61,2±4,66%). Simpulan: IHH berkaitan dengan desaturasi oksigen dan perubahan biomarker stres oksidatif sirkulasi. Pola MDA dan GSH yang tidak linear konsisten dengan respons redoks yang bergantung waktu, tetapi belum membuktikan adaptasi fisiologis.