Disertasi

Pengaruh Pajanan Hipoksia Hipobarik Intermiten terhadap Stres Oksidatif, Perubahan Tunika Media di Arteri Pulmonal, serta Kadar Protein SLR 11 dan HIF-1α pada Tikus Sprague-Dawley = The Effect of Intermittent Hypobaric Hypoxia Exposure on Oxidative Stress, Pulmonary Artery Tunica Media Changes, and sLR11 and HIF-1α Serum Levels : Study in Spague Dawley mice.

Hipoksia hipobarik intermiten (HHI) merupakan kondisi yang sering dialami oleh awak penerbang dan personel yang bekerja pada ketinggian. Meskipun hipoksia kronik diketahui memicu remodeling vaskular pulmonal, perubahan biokimia dan morfologi akibat pajanan hipobarik singkat berulang belum banyak diteliti. Penelitian ini bertujuan menilai stres oksidatif (MDA–GSH), aktivasi jalur hipoksia (HIF-1α), ekspresi sLR11, serta perubahan ketebalan tunika media arteri pulmonal pada model HHI. Penelitian ini bertujuan mengevaluasi efek HHI durasi pendek terhadap stres oksidatif (MDA dan GSH), aktivasi jalur hipoksia (HIF-1α), ekspresi sLR11, serta perubahan ketebalan tunika media arteri pulmonal pada tikus. Penelitian eksperimental ini menggunakan 25 ekor tikus jantan Sprague–Dawley dengan berat badan awal homogen yang dibagi menjadi lima kelompok: kontrol dan empat kelompok hipoksia hipobarik intermiten (HHI). Perlakuan HHI dilakukan pada ketinggian simulasi 25.000 kaki selama 5 menit per hari selama 1 , 3, 7, dan 1 4 hari menggunakan hypobaric chamber. Berat badan tikus dipantau selama penelitian. Setelah perlakuan, diambil jaringan arteri pulmonal dan sampel darah. Kadar malondialdehida (MDA) dan γ-glutamyl-cysteinyl-glycine (GSH) diukur secara spektrofotometri menggunakan metode Wills dan Ellman. Kadar protein serum HIF-1α dan soluble LR11 (sLR11) dianalisis dengan metode ELISA. Ketebalan tunika media arteri pulmonal dinilai secara histopatologis. Data dianalisis secara statistik. Pajanan HHI meningkatkan MDA dan menurunkan GSH secara bermakna. Terjadi peningkatan kadar HIF-1α dan sLR11 yang menunjukkan aktivasi jalur hipoksia dan respons remodeling vaskular. Ketebalan tunika media arteri pulmonal meningkat terutama pada kelompok HHI 3× dan 14×, mencerminkan proses remodeling vaskular dini. Pajanan HHI durasi pendek dan berulang mampu menyebabkan stres oksidatif, aktivasi jalur HIF-1 α/sLR1 1 , serta remodeling awal vaskular pulmonal. Studi ini menunjukkan bukti awal bahwa pajanan hipobarik singkat 25.000 kaki selama 5 menit, bila diulang, telah cukup untuk memicu perubahan biokimia dan struktural vaskular, serta menonjolkan sLR11 sebagai kandidat biomarker dini remodeling vaskular akibat hipoksia.
Kata Kunci: arteri pulmonal, hipoksia hipobarik intermiten, HIF-1 α, remodeling vaskular, sLR11, stres oksidatif.


Intermittent hypobaric hypoxia (IHH) is commonly experienced by aircrew and high-altitude personnel. While chronic hypoxia is known to induce pulmonary vascular remodeling, the biological impact of short-duration repeated hypobaric exposure remains poorly understood. This study aimed to evaluate the effects of short-duration IHH on oxidative stress status (MDA and GSH), activation of hypoxia-related pathways (HIF-1 α), sLR1 1 expression, and structural changes of the pulmonary artery in rats. This experimental study used 25 male Sprague– Dawley rats with homogeneous baseline body weights, divided into five groups: a control group and four intermittent hypobaric hypoxia (IHH) groups. IHH exposure was performed at a simulated altitude of 25,000 ft for 5 minutes per day over 1 , 3, 7, and 14 days using a hypobaric chamber, with body weight monitored throughout the study. After exposure, pulmonary artery tissue and blood samples were collected. Malondialdehyde (MDA) and γ-glutamyl-cysteinyl-glycine (GSH) levels were measured spectrophotometrically using the Wills and Ellman methods, respectively. Serum HIF-1α and soluble LR11 (sLR11) concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). Pulmonary artery media thickness was evaluated histopathologically. Statistical analysis was performed to assess differences among groups. IHH significantly increased oxidative stress marked by elevated MDA and reduced GSH. Serum HIF-1 α and sLR11 levels showed notable activation trends reflecting hypoxia-induced vascular signaling. Media thickness of the pulmonary artery increased particularly in the 3× and 1 4× exposure groups, indicating early vascular remodeling. Short, repeated hypobaric hypoxia can induce oxidative stress, activate HIF-1 α/sLR1 1 pathways, and promote pulmonary vascular remodeling. This study provides one of the first experimental proofs that brief intermittent exposure at 25,000 ft for only 5 minutes, when repeated, is sufficient to trigger biochemical and structural vascular alterations, highlighting sLR1 1 as a potential early biomarker of hypoxia-induced pulmonary remodeling.
Keywords: HIF-1α, intermittent hypobaric hypoxia, oxidative stress, sLR11, Pulmonary artery, vascular remodelling.