Potensi Proteksi Buah Tin (Ficus carica) dan Olahraga Aerobik Terhadap Degenerasi Hipokampus Tikus Model Inflamasi dengan Hipoksia : Kajian terhadap ekspresi mRNA gen Proliferating Cell Nuclear Antigen (PCNA), Protein 53 (P53) dan gambaran histologi pada hipokampus tikus Sprague-Dawley

Indira Rahmana Razak, dr. R. Jajar Setiawan, M. Sc, Ph.D; dr. Andreanyta Meliala, Ph.D, AIFM

2025 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar Belakang: Kesehatan otak merupakan aspek penting dalam menentukan kualitas hidup dan kognisi seseorang, namun rentan terhadap gangguan akibat inflamasi dan hipoksia. Inflamasi adalah respon biologis terhadap cedera atau infeksi yang ditandai oleh pelepasan mediator seperti TNF-?, IL-6, dan prostaglandin. Hipoksia merupakan kondisi rendahnya suplai oksigen ke jaringan yang dapat menyebabkan stres oksidatif dan kerusakan sel. Kombinasi inflamasi dan hipoksia sering dijumpai pada kondisi patologis seperti ISPA, sepsis, atau penyakit neurodegeneratif seperti Alzheimer, di mana gangguan sawar darah otak dan akumulasi beta-amiloid memperparah kerusakan saraf. Faktor eksternal seperti olahraga berlebihan, polusi udara, kurang tidur, dan defisiensi nutrisi juga dapat memicu respons inflamasi dan hipoksia. Oleh karena itu, pendekatan preventif melalui intervensi gaya hidup sehat, seperti olahraga aerobik intensitas sedang dan konsumsi pangan fungsional kaya antioksidan seperti buah tin (Ficus carica), berpotensi menekan stres oksidatif dan meningkatkan perlindungan otak melalui aktivasi jalur molekuler seperti Nrf2 dan HIF-1?.

Tujuan: Mengetahui pengaruh kombinasi puree buah tin (PBT) dan olahraga aerobik terhadap ekspresi gen PCNA, P53, dan gambaran histologis hipokampus tikus model inflamasi yang diperparah dengan hipoksia.

Metode: Penelitian kuasi eksperimental dengan post test only controlled group design menggunakan 24 ekor tikus jantan dibagi dalam 6 kelompok perlakuan: 1. kontrol sehat, 2. kontrol sakit (LPS + hipoksia), 3. PBT + LPS +hipoksia, 4. Olahraga + LPS + hipoksia, 5. PBT + olahraga + LPS + hipoksia, 6. PBT + olahraga + hipoksia. Intervensi dilakukan selama 11 minggu. Pengukuran dilakukan terhadap sickness behavior, ekspresi gen PCNA dan P53 (RT-PCR), serta jumlah sel piknosis dengan pewarnaan histologi hipokampus (HE staining). Data dianalisis menggunakan ANOVA dan LSD (p<0>

Hasil: Kelompok kombinasi PBT dan olahraga menunjukkan ekspresi PCNA tertinggi pada kelompok 4 dan P53 terendah pada kelompok 6. Gambaran histologis hipokampus juga menunjukkan struktur yang sel dengan lebih sedikit kerusakan pada kelompok 6 dibanding kontrol sakit.

Kesimpulan: Kombinasi puree buah tin dan olahraga aerobik intensitas sedang terbukti memberikan efek protektif terhadap degenerasi hipokampus dengan meningkatkan regenerasi sel melalui ekspresi gen PCNA yang lebih tinggi, menekan sinyal stres seluler melalui ekspresi gen P53 yang lebih rendah dibandingkan dengan kontrol sakit, dan memperbaiki struktur jaringan hipokampus.

Background: Brain health is an important aspect in determining a person's quality of life and cognition, but is vulnerable to disorders due to inflammation and hypoxia. Inflammation is a biological response to injury or infection characterized by the release of mediators such as TNF-?, IL-6, and prostaglandins. Hypoxia is a condition of low oxygen supply to tissues that can cause oxidative stress and cell damage. The combination of inflammation and hypoxia is often found in pathological conditions such as ARI, sepsis, or neurodegenerative diseases such as Alzheimer's, where disruption of the blood-brain barrier and accumulation of beta- amyloid exacerbate nerve damage. External factors such as excessive exercise, air pollution, lack of sleep, and nutritional deficiencies can also trigger inflammatory and hypoxic responses. Therefore, a preventive approach through healthy lifestyle interventions, such as moderate-intensity aerobic exercise and consumption of functional foods rich in antioxidants such as figs (Ficus carica), has the potential to suppress oxidative stress and increase brain protection through activation of molecular pathways such as Nrf2 and HIF-1?. Objective: To determine the effect of the combination of fig puree (PBT) and aerobic exercise on the expression of PCNA, P53 genes, and histological features of the hippocampus of rats in an inflammatory model exacerbated by hypoxia.

Methods: Quasi-experimental study with post-test only controlled group design using 24 male rats divided into 6 treatment groups: 1. healthy control, 2. sick control (LPS + hypoxia), 3. PBT + LPS + hypoxia, 4. Exercise + LPS + hypoxia, 5. PBT + exercise + LPS + hypoxia, 6. PBT + exercise + hypoxia. The intervention was carried out for 11 weeks. Measurements were made on sickness behavior, PCNA and P53 gene [removed]RT-PCR), and the number of pyknosis cells with hippocampal histology staining (HE staining). Data were analyzed using ANOVA and LSD (p <0>

Results: The combination group of PBT and exercise showed the highest PCNA expression in group 4 and the lowest P53 in group 6. Histological features of the hippocampus also showed a cellular structure with less damage in group 6 compared to diseased controls.

Conclusion: The combination of fig puree and moderate intensity aerobic exercise has been shown to provide a protective effect against hippocampal degeneration by increasing cell regeneration through higher PCNA gene expression, suppressing cellular stress signals through lower P53 gene expression compared to diseased controls, and improving hippocampal tissue structure.

Kata Kunci : Fig Puree, Treadmill, Lipopolysaccharide, Hypoxia, Sickness Behavior.