Effect of Exercise, Metformin, and Their Combination on Ki-67 Expression and Endometriotic Implants in a Mouse Model of Endometriosis

Objective: To determine the effects of exercise, metformin, and their combination on Ki-67 expression and endometriotic implants in a mouse model of endometriosis.

This experimental study used 28 three-month-old BALB/c mice with induced endometriosis, which were randomly and equally divided into four groups (K, P1, P2, and P3). On day 15, group P1 received a swimming protocol (10 minutes/day) for 14 days, group P2 received metformin (4 mg/day) for 14 days, and group P3 received a combination of both treatments, while group K served as the control and received no treatment. Immunohistochemical analysis of Ki-67 expression was performed on peritoneal tissues from the abdominal and pelvic cavities and measured using the Remmele Scale Index. Endometriotic implant areas were analyzed using a computer-based tracing method. Statistical analysis was performed using SPSS version 32, with significance set at p < 0.05.

There were significant differences in Ki-67 expression (p = 0.002) and endometriotic implant area (p < 0.001) among the groups. Ki-67 expression was significantly lower in the P1 group compared to the other groups, while the implant area was significantly lower in the P2 group compared to the other groups.

Exercise and metformin may be effective potential treatments for endometriosis by reducing Ki-67 expression and endometriotic implant size. Pengaruh Olahraga, Metformin dan Kombinasi terhadap Ekspresi Ki-67 dan Implantasi Endometriosis pada Mencit Model Endometriosis Abstrak Tujuan: Penelitian ini bertujuan untuk menentukan pengaruh olahraga, metformin, dan kombinasinya terhadap ekspresi Ki-67 dan implan endometriotik pada model mencit endometriosis. Metode: Penelitian ini menggunakan metode penelitian eksperimental dengan menggunakan 28 ekor mencit BALB/c berumur tiga bulan dengan endometriosis yang diinduksi, yang dibagi secara acak dan merata menjadi empat kelompok (K, P1, P2, dan P3). Pada hari ke-15, kelompok P1 diberikan protokol renang (10 menit/hari) selama 14 hari, kelompok P2 diberikan metformin (4 mg/hari) selama 14 hari, dan kelompok P3 diberikan kombinasi kedua perlakuan, sedangkan kelompok K sebagai kontrol tidak diberikan perlakuan. Analisis imunohistokimia ekspresi Ki-67 dilakukan pada jaringan peritoneum rongga abdomen dan pelvis, serta diukur menggunakan Indeks Skala Remmele. Luas implan endometriotik dianalisis menggunakan metode penelusuran berbasis komputer. Analisis statistik dilakukan menggunakan SPSS versi 32 dengan tingkat signifikansi p < 0,05. Hasil: Hasil penelitin ini menunjukkan bahwa terdapat perbedaan bermakna pada ekspresi Ki-67 (p = 0,002) dan luas implan endometriotik (p < 0,001) antar kelompok. Ekspresi Ki-67 secara signifikan lebih rendah pada kelompok P1 dibandingkan kelompok lainnya, sedangkan luas implan secara signifikan lebih rendah pada kelompok P2 dibandingkan kelompok lainnya. Kesimpulan: Olahraga dan metformin berpotensi menjadi terapi yang efektif untuk endometriosis dengan menurunkan ekspresi Ki-67 dan ukuran implan endometriotik.

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