UPREGULATION OF ENDOTHELIN CONVERTING ENZYME-1 CORRELATES WITH TUBULAR INJURY AND KALLIKREIN REDUCTION IN KIDNEY FIBROSIS MODEL IN MICE

GHASSANI ADANI R, dr.Nur Arfian, Ph.D.; dr.Santosa Budiharjo,M.Kes.,PA(K).

2015 | Skripsi | S1 PENDIDIKAN DOKTER

LATAR BELAKANG: Gagal Ginjal Kronis merupakan salah satu beban penyakit tertinggi di dunia. Fibrosis ginjal menjadi tolak ukur untuk megetahui adanya Gagal Ginjal Kronis. Endothelin-1(ET-1) dan Endothelin Converting Enzyme-1(ECE-1) diduga memegang peranan penting dalam fibrosis ginjal. Para peneliti telah mengobservasi ET-1 yang ternyata dapat menurunkan kecepatan progresi cedera ginjal; namun peran ECE-1 sebagai enzim konverter belum pernah diteliti sebelumya. TUJUAN: Menelaah hubungan ekspresi Endothelin Converting Enzyme-1, cedera tubulus dan ekspresi kallikrein. METODE: Mencit jantan galur Swiss diberi perlakuan Obstruksi Ureter Unilateral untuk menginduksi fibrosis ginjal. Operasi Sham dilakukan pada grup kontrol (SO) (n=5). Mencit diterminasi pada hari ke-7(D7UUO; n=5) dan hari ke 14(D14UUO; n=5) setelah operasi. Skor cedera tubulus dihitung berdasarkan pewarnaan Periodic Acid Schiff (PAS). Expresi ECE-1 dan kallikrein diobservasi dengan menggunakan reverse transcriptase PCR (RT-PCR). HASIL: Obstruksi Ureter Unilateral menginduksi kenaikan skor cedera tubulus pada D7UUO dan D14UUO(p < 0,05 VS SO), kemudian diikuti dengan kenaikan ekspresi ECE-1 pada D14UUO (p < 0,05 VS SO),serta penurunan kallikrein pada D7UUO dan D14UUO (p < 0,05 VS SO). KESIMPULAN : Kenaikan ekspresi ECE-1 berkorelasi kuat secara positif dengan cedera tubulus, namun tidak berkorelasi dengan penurunan kallikrein. KATA KUNCI : Gagal Ginjal Kronis, Cedera Tubulus, ECE-1, Kallikrein, Obstruksi Ureter Unilateral.

BACKGROUND: Chronic Kidney Disease (CKD) become one of the highest burden of disease in the world. Kidney fibrosis becomes the hallmark of CKD. Endothelin-1(ET1) and Endothelin Converting Enzyme-1(ECE-1) may play role in kidney fibrosis. Some research observing ET-1 showing beneficial effect for slowing kidney injury progress; but the ECE-1 as the converter enzyme of ET-1 has not been studied yet. PURPOSE: to elucidate the corelation between Endothelin Converting Enzyme-1 expression, Tubular Injury and Kallikrein expression. METHOD: We performed Unilateral Uretheral Obstruction(UUO) in male background Swiss mice to induce kidney fibrosis. Sham operation was performed to control group (SO) (n=5). Mices were sacrificed in day 7 (D7UUO; n=5) and day 14 (D14UUO; n=5) after operation. Tubular injury score was quantified based on Periodic Acid Schiff (PAS) staining. We performed reverse transcriptase PCR (RT-PCR) to examine ECE-1 and Kallikrein expression. RESULT: Unilateral Uretheral Obstruction(UUO) induced an increased of tubular injury scoring in D7UUO and D14UUO(p < 0,05 VS SO), and followed by the increasing of ECE-1 Expression in D14UUO (p < 0,05 VS SO), also reduction of Kallikrein in D7UUO and D14UUO (p < 0,05 VS SO). CONCLUSION : We revealed that upregulation of ECE-1 has strong positive corelation with Tubular Injury, whereas it has no significant corelation with reduction of Kallikrein.

Kata Kunci : Chronic Kidney Disease, Tubular Injury, ECE1, Kallikrein, Unilateral Uretheral Obstruction.