Pengaruh Pemberian Ekstrak Pegagan (Centella asiatica sp.) terhadap Fibrosis Interstisium, Ekspresi HGF, dan Ekspresi BMP-7 pada Mencit dengan Nefrektomi Subtotal 5/6

TIARA GITAMI PUTRI, dr. Nur Arfian, PhD; Dr. dr. Dwi Cahyani Ratna Sari, M.Kes., PA(K)

2017 | Skripsi | S1 PENDIDIKAN DOKTER

Latar Belakang: Gagal ginjal kronis memiliki karakteristik berupa fibrosis dengan kerusakan arsitektur ginjal. Hepatocyte growth factor (HGF) dan bone morphogenic protein-7 (BMP-7) merupakan faktor antifibrosis endogen ginjal. Centella asiatica (CeA) merupakan tanaman herbal yang diketahui dapat menurunkan fibrosis. Tujuan Penelitian: Mengkaji pengaruh CeA terhadap fibrosis interstisium, ekspresi HGF, dan ekspresi BMP-7 pada model nefrektomi subtotal 5/6 (SN). Metode Penelitian: Gagal ginjal kronis diinduksi dengan prosedur SN pada 15 ekor mencit galur Swiss jantan (2 bulan, 30-40 gram) dan diterminasi setelah 7 hari observasi (SN 7, n=5). Sham operation digunakan sebagai kontrol (SO, n=5). CeA dengan dosis 840 mg/kgBB/hari peroral diberikan kepada mencit SN (SN 7 CeA, n=5). Ginjal setiap mencit diambil untuk pemeriksaan kuantifikasi fibrosis interstisium berdasarkan pewarnaan Sirius Red dan untuk ekstraksi RNA. Ekspresi HGF dan BMP-7 dihitung dengan Reverse Transcripase-PCR. Hasil: Prosedur SN pada kelompok SN 7 menginduksi fibrosis interstisium yang lebih tinggi (p<0,01) dan ekspresi HGF dan BMP-7 yang lebih rendah (p<0,05) dibandingkan kelompok SO. Pada kelompok SN 7 CeA, fibrosis interstisium lebih rendah (p<0,01) dan ekspresi BMP-7 lebih tinggi (p>0,05) dibandingkan kelompok SN 7. Terdapat korelasi negatif sangat kuat yang bermakna (r=-0,943, p=0,005) antara fibrosis interstisium dengan ekspresi BMP-7. Terdapat korelasi tidak signifikan antara fibrosis intestisium dengan ekspresi HGF (r=-0,574, p=0,178). Kesimpulan: Centella asiatica diduga menurunkan fibrosis interstisium melalui peningkatan ekspresi BMP-7 di gagal ginjal kronis. Kata Kunci : Centella asiatica, SN, fibrosis ginjal, HGF, BMP-7.

Background: Chronic kidney disease (CKD) is characterized by kidney fibrosis with destruction of renal architecture. Hepatocyte Growth Factor (HGF) and Bone Morphogenic Protein-7 (BMP-7) are endogenous antifibrotic factors. Centella asiatica (CeA) is herbaceous plant that is well known to decrease fibrosis, although in kidney fibrosis is remain unknown. Research Objectives: This study is to elucidate effect of CeA on interstitial fibrosis, HGF expression, and BMP-7 expression in 5/6 subtotal nephrectomy (SN) model. Research Methods: CKD was induced using 5/6 SN procedure in male Swiss-background mice (2 months, 30-40 grams), then the mice were terminated in day 7 (SN 7 group, n=5). Sham operation was used as control (SO, n=5). CeA treatment with dose 840 mg/kg orally per day was given in SN mice (SN 7 CeA, n=5). Kidneys were harvested for interstitial fibrosis quantification based on Sirius Red staining and for RNA extraction. Reverse Transcriptase-PCR (RT-PCR) was used to quantify HGF and BMP-7 expression. Results: SN induced interstitial fibrosis with higher collagen area fraction (p<0.01) and reduction of HGF and BMP-7 expression in SN7 group compared to SO. Meanwhile, SN 7 CeA had significant lower interstitial fibrosis (p<0,01) and higher BMP-7 expression (p<0,05) compared to SN 7 group. There was significant and very strong negative corellation (r=-0,943, p=0,005) between interstitial fibrosis and BMP-7 expression. However, there was no significant correlation between interstitial fibrosis and HGF expression(r=-0,574, p=0,178). Conclusion: Centella asiatica may decrease interstitial fibrosis through upregulating BMP-7 expression in CKD. Keywords: Centella asiatica, SN, kidney fibrosis, HGF, BMP-7.

Kata Kunci : Centella asiatica, SN, fibrosis ginjal, HGF, BMP-7