PENGARUH VITAMIN D TERHADAP VASCULAR REMODELING DAN EKSPRESI ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS) DAN PREPROENDOTHELIN-1 (PPET-1) PADA MENCIT MODEL UNILATERAL URETERAL OBSTRUCTION

SAGITA MEGA SEKAR KENCANA, dr. Nur Arfian, Ph.D.; dr. Santosa Budihardjo, M.Kes., PA(K)

2016 | Skripsi | S1 PENDIDIKAN DOKTER

Latar Belakang: Penderita chronic kidney disesase (CKD) saat ini mengalami peningkatan di Indonesia maupun dunia. ET-1 dan eNOS diduga terlibat dalam progresi CKD dimana keduanya berperan dalam regulasi vasa. Bentuk aktif Vitamin D, calcitriol diduga memiliki efek renoprotektif. Namun, hingga saat ini belum banyak diketahui peran calcitriol dalam regulasi ET-1, eNOS, dan vascular remodeling. Tujuan: Penelitian ini bertujuan untuk mengetahui peran Vitamin D dalam vascular remodeling melalui modulasi ET-1 dan eNOS pada mencit dengan Unilateral Ureteral Obstruction (UUO). Metode: Mencit jantan galur Swiss Webster (n=15, usia 3-4 bulan, berat 30-40 g) dibagi dalam 3 kelompok: kontrol (SO), UUO 7 hari tanpa Vitamin D (UUO), dan UUO 7 hari dengan Vitamin D (UUOD). Pada hari ke-7, mencit diterminasi kemudian dilakukan pengambilan sampel untuk ekstraksi cDNA dan blok parafin. Remodeling vasa dinilai dengan pengecatan Sirius Red dengan parameter area lumen dan lumen-to-wall area ratio (LWAR). Ekspresi PPET-1 dan eNOS dinilai menggunakan RT-PCR. Hasil: Didapatkan penurunan area lumen, LWAR dan peningkatan ekspresi PPET-1 (p<0,05) tanpa perbedaan bermakna pada ekspresi eNOS pada kelompok UUO dibandingkan dengan SO. Sedangkan dibanding UUO, pada kelompok UUOD didapatkan nilai yang lebih tinggi untuk ekspresi eNOS (p<0,05) tanpa perbedaan bermakna pada area lumen, LWAR dan ekspresi ET-1. Kesimpulan: Vitamin D mempengaruhi vascular remodeling melalui modulasi eNOS tanpa melalui jalur ET-1.

Background: Increased prevalention of patient with chronic kidney disease (CKD) is happening not only in Indonesia but also globaly. ET-1 and eNOS are known to be involved in CKD progression where both have role on vascular regulation. Active form of Vitamin D, calcitriol are suggested to have renoprotective effect. However, the role of calcitriol on ET-1 and eNOS regulation marked by vascular remodeling is not clearly understood. Aim: This study is aimed to elucidate the role of Vitamin D in vascular remodeling through ET-1 and eNOS modulation in mice with unilateral ureteral obstruction (UUO). Method: Male Swiss-Webster background mice (n=15, 3-4 months old, weighted 30-40 g) was divided into three gropus: sham-operated (SO), 7 days UUO without Vitamin D (UUO), and 7 days UUO with Vitamin D (UUOD). Termination was done at day 7, and the obstructed kidney was harvested for paraffin making and cDNA extraction. Vascular remodeling was assessed by measuring lumen area and lumento- wall area ratio (LWAR) microscopically with Sirius Red staining. The expression of PPET-1 and eNOS was quantified using RT-PCR. Results: UUO7 group demonstrated lower lumen area, LWAR and higher PPET-1 expression (p<0,05), but no significance difference in eNOS expression compared to SO. While compared to UUO, UUOD group demonstrate higher eNOS expression (p<0,05), but no significance difference in lumen area, LWAR and PPET-1 expression. Conclusion: Vitamin D is suggested to have a role in vascular remodeling via eNOS modulation independent ET-1 pathway.

Kata Kunci : CKD, calcitriol, vascular remodeling, PPET-1, eNOS