Correlation between expression of Toll Like Receptor 4 (TLR 4) and glomerulosclerosis in 5/6 Nephrectomy in mice

SASKIA OCTARIZA, dr. Nur Arfian, Ph.D. ; dr. Dian Prasetyo Wibisono, M.Sc.

2016 | Skripsi | S1 PENDIDIKAN DOKTER

LATAR BELAKANG: gagal ginjal kronik menjadi masalah bagi kesehatan masyarakat secara global karena prevalensi dan konesekuensi dari penyakit tersebut, seperti penyakit kardiovaskular, gagal ginjal tahap akhir dan juga kematian prematur. Saat ini toll like receptor 4 telah ditemukan mempunyai korelasi dengan fibrosis di beberapa organ, hal tersebut mengindikasikan TLR 4 juga mempunyai peran dalam glomerulosclerosis mengingat glomerulus juga mengekspresikan TLR 4. TUJUAN; untuk mengetahui korelasi antara ekspresi toll like receptor 4 dengan glomerulosclerosis METODE: kami melakukan prosedur 5/6 subtotal nefrektomi pada mencit jantan jenis Swiss untuk menginduksi glomerulosklerosis. Operasi sham dilakukan untuk kontrol grup (SO) (n=5). Mencit dikorbankan di hari ke 7 (D7 5/6 SN; n=5) dan di hari ke 28 (D28 5/6 SN; n=5) setelah 5/6 nefrektomi dilakukan. Skor glomerulosklerosis dikuantifikasi berdasarkan pengecatan Periodic Acid Schiff (PAS). Ekspresi toll like receptor 4 diukur dengan menggunakan RT-PCR setelah ginjal diekstrasi terlebih dahulu. RESULT: 5/6 subtotal nefrektomi menginduksi kenaikan skor glomerulosklerosis di D7 5/6 SN dan D28 5/6 SN dengan diikuti kenaikan ekpresi TLR 4 di D7 5/6 SN dan pengurangan ekspres di D28 5/6 SN. KESIMPULAN: skor glomerulosklerosis mempunyai korelasi yang kuat dengan TLR 4 di D7 tetapi tidak signifikan di D28.

BACKGROUND: CKD become burden for the global public health because of its prevalence and consequence of the disease, such as cardiovascular disease, end stage renal disease, and also premature death. Recently toll like receptor 4 has been found to have correlation with fibrosis in several organs, it may indicate TLR 4 has role in glomerulosclerosis since glomerulus also express TLR 4. PURPOSE: To elucidate the correlation between toll like receptor 4 expression with glomerulosclerosis METHOD: We performed 5/6 subtotal nephrectomy in male strain Swiss mice to induce glomerulosclerosis. Sham operation was performed to control group (SO) (n=5). The mice were sacrificed in day 7(D7 5/6 SN; n=5) and day 28 (D28 5/6 SN; n=5) after 5/6 subtotal nephrectomy procedure. Glomerulosclerosus score was quatified based on Periodic Acid Schiff (PAS) staining. Toll like receptor 4 expression was measured using RT-PCR after the kidney being extracted. RESULT: 5/6 Subtotal nephrectomy (5/6 SN) induced an increase of glomerulosclerosis score in D7 5/6 SN and D28 5/6 SN, followed by increase of TLR4 expression in D7 5/6 SN and decrease of its expression in D28 5/6 SN. CONCLUSION: Glomerulosclerois score has positive strong correlation in D7 but not significant in D28

Kata Kunci : Chronic Kidney Disease, Glomerulosclerosis, TLR 4, mice, 5/6 subtotal nephrectomy