AKTIVITAS KEMBANG MENTEGA (Nerium indicum Mill) TERHADAP EKSPRESI TRANSFORMING GROWTH FACTOR-BETA1 (TGF-Beta1) DAN VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) PADA FIBROBLAS KELOID

HERNITA TAURUSTYA, Prof. Dr. Mae Sri Hartati Wahyuningsih, M.Si., Apt.; Dr. dr. Med. Indwiani Astuti

2019 | Tesis | MAGISTER ILMU BIOMEDIK

Latar belakang: Keloid merupakan tumor jinak fibroproliferatif dermis dengan ciri terjadinya peningkatan growth factor sehingga menginduksi proliferasi fibroblas, migrasi dan sintesis kolagen yang berlebihan. Transforming growth factor-beta1 (TGF-Beta1) dan Vascular Endothelial growth factor (VEGF) berperan penting dalam patogenesis keloid. Ekstrak Nerium indicum Mill telah banyak diteliti sebagai agen terapi keloid. 5+--oleandrin yang terkandung di dalam N.indicum mempunyai aktivitas antikeloid dengan menghambat proliferasi fibroblas keloid, migrasi fibroblas, deposisi kolagen dan sintesis TGF-Beta1. Penelitian lebih lanjut diperlukan untuk mengetahui mekanisme aksi molekuler N.indicum dalampenatalaksanaan keloid. Tujuan penelitian: Penelitian ini bertujuan untuk mengetahui efek pemberian ekstrak N.indicum terhadap ekspresi TGF-Beta1 dan VEGF pada fibroblas keloid. Metode: Penelitian ini merupakan studi in vitro rancangan eksperimental semu (quasi experimental) dengan post test only controlled group design. Subjek penelitian adalah sel fibroblas keloid subkultur passage IV-VII yang diisolasi dari jaringan kulit pasien keloid dengan tekhnik explant. Kelompok perlakuan mendapatkan ekstrak N.indicum dengan serial konsentrasi 2mcg/ml, 1mcg/ml, 0,5mcg/ml dan kelompok kontrol hanya mendapatkan medium. Supernatan didapatkan setelah masa inkubasi 72 jam. Pemeriksaan ekspresi TGF-Beta1 dan VEGF pada kultur fibroblas keloid menggunakan prosedur ELISA. Hasil penelitian: Ekspresi TGF-Beta1 pada kelompok perlakuan ekstrak N.indicum (2mcg/ml, 1mcg/ml, 0,5 mcg/ml) secara signifikan lebih rendah dibandingkan dengan kelompok kontrol medium fibroblas keloid (p<0,05). Semakin tinggi konsentrasi ekstrak N.indicum semakin rendah kadar TGF-Beta1. Ekspresi VEGF pada kelompok perlakuan ekstrak N.indicum lebih rendah dibandingkan dengan kelompok kontrol medium fibroblas keloid. Penurunan kadar VEGF fibroblas keloid secara signifikan terjadi pada konsentrasi ekstrak 2mcg/ml dan 1mcg/ml (p<0,05). Kesimpulan: Ekspresi TGF- dan VEGF pada kelompok perlakuan ekstrak N.indicum lebih rendah jika dibandingkan dengan kelompok kontrol fibroblas keloid.

Background: Keloid is a benign fibroproliferative dermis tumor characterized by increase in growth factor which induce fibroblast proliferation, excessive migration and synthesis of collagen. Transforming growth factor-Beta1 (TGF-Beta1) and Vascular endothelial growth factor (VEGF) plays a pivotal role in keloid pathogenesis. Nerium indicum Mill extract had been studied as keloid therapy agent. 5+--oleandrin contained in N.indicum has antikeloid activity by inhibiting keloid fibroblast proliferation, fibroblast migration, collagen deposition and TGF-Beta1 synthesis.Further research is needed to explore molecular mechanism of N.indicum in keloid management. Objective: This study aims to determine the effect of administration N.indicum extract to TGF-Beta1 and VEGF expression on keloid fibroblast. Method: This research was in vitro quasi experimental study with post test only controlled group design. The research subjects were fibroblast cells passage IV-VII isolated from patients keloid tissue with explant techniques. Treatment grups receive N.indicum extract with serial concentration of 2mcg/ml, 1mcg/ml, 0,5mcg/ml, and control grup receive medium only. The supernatant were obtained after 72 hours incubation period. Examination of TGF-Beta1 and VEGF expressions were measure using ELISA procedure. Result: The expression of TGF-Beta1 in the treatment groups extract N.indicum (2mcg/ml, 1mcg/ml, 0,5mcg/ml) were significantly lower than the control group of keloid fibroblasts (p <0,05), according to increased concentration. VEGF expression in the treatment groups of N.indicum extract were lower than the control group of keloid fibroblasts. A significant decrease in keloid fibroblast VEGF levels occurred at extract concentrations of 2mcg/ml and 1mcg/ml (p <0,05). Conclusion: The expression of TGF-Beta1 and VEGF in the treatment group of N.indicum extract was lower than the control group keloid fibroblast.

Kata Kunci : Fibroblas keloid, Nerium indicum Mill, Oleandrin, TGF-Beta1, VEGF, Keloid fibroblasts, Nerium indicum Mill, Oleandrin, TGF-Beta1, VEGF