PENGARUH PEMBERIAN N-ASETILSISTEIN TERHADAP EKSPRESI CASPASE-1 GLOMERULUS DAN DERAJAT KERUSAKAN GINJAL PADA MENCIT NEFRITIS LUPUS INDUKSI PRISTAN

Anindita Rachmawati, Bambang Purwanto, Diding Heri Prasetyo

DOI: https://doi.org/10.23917/biomedika.v10i2.7015

Abstract

ABSTRAK

Lupus nefritis (LN) terkait dengan penebalan membran basal glomerulus. Pengendapan kompleks imun  memicu kaskade respon inflamasi disertai aktivasi reactive oxygen species (ROS), akhirnya terjadi aktivasi caspase-1, dan caspase-1, mengaktifkan IL-1B dan IL-18 yang berlanjut terjadinya apoptosis dan nekrosis dan akhirnya terjadi kerusakan ginjal. Peningkatan ekspresi caspase-1 dapat dicegah oleh N-Asetil Sistein (NAS), yang merupakan suatu senyawa dengan efek antioksidan dan antiinflamasi. Penelitian ini bertujuan untuk mengetahui pengaruh NAS terhadap ekspresi caspase-1 dan terjadinya apoptosis dan nekrosis ginjal pada mencit model lupus nefritis. Penelitian ini merupakan penelitian eksperimental laboratoris, dengan sampel 24 ekor mencit Balb/C betina yang dibagi menjadi kelompok kontrol, LN, dan LN+NAS. Untuk membuat model LN, hewan coba diberikan injeksi 0,5 ml pristan intraperitoneal dosis tunggal. NAS diberikan secara peroral dengan dosis 4,7 mg/hari) selama delapan minggu. Mencit kontrol tidak diinokulasi selama penelitian. Ekspresi caspase-1 dihitung dari 100 sel makrofag yang immunoreaktif dengan teknik imunohistokimia dan kejadian apoptosis dan nekrosis dihitung dengan dengan teknik histopatologi. Hasil penelitian menunjukkan bahwa, pemberian NAS menurunkan ekspresi caspase-1 (22,8 ± 6,4 vs 31,4 ± 7,5 per 100 sel makrofag imunoreaktif; p = 0,000)  dan menurunkan kerusakan ginjal (6,75 ± 2,92 vs 9,88 ± 3,56; p =0,010) dibandingkan kelompok LN. NAS secara bermakna menurunkan ekspresi caspase-1 dan derajat kerusakan ginjal pada mencit model LN.

Kata Kunci: Caspase-1, Derajat Kerusakan Ginjal, Lupus Nefritis, Pristan

 

ABSTRACT

Lupus nephritis (LN) associated with thickening of the basal membrane of the glomerulus. The deposition  of immune complexes trigger a cascade of inflammatory response accompanied the activation of reactive oxygen species (ROS), finally happened activation caspase-1, and enable the IL-1B and IL-18 to be the active form, and to be continued into occurrence of apoptosis and necrosis and eventually the kidney injury. Increased of caspase-1 expression can be prevented by N-Acetyl Cysteine (NAS), which is a compound with antioxidant and anti-inflammatory effects.This study aimed to analyze the effects of NAS on the expression of Caspase-1 and degree of renal injury in mice models of lupus nephritis. This study is an experimental research laboratory, with a sample of 24 females Balb/C mice were divided into a control group, LN and LN+NAS. To create a model LN, experimental animals given intraperitoneal injection of 0.5 ml Pristan single dose. NAS administered orally at a dose of 4.7 mg/day for eight weeks. Control mice not inoculated during the study. Expression of Caspase-1 was calculated from 100 macrophage cells immunoreactive with immunohistochemical and degree of renal injury with histopathological techniques. One way analysis of variance (Anova) for caspase-1 expression and degree  of renal injury, and p<0.05 were used to determine the significant differences. The provision of NAS decreased the expression of caspase-1 (22,8 ± 6,4 vs 31,4 ± 7,5  per 100 macrophage immunoreactive cells; p = 0.042) and degree of renal injury (6,75 ± 2,92 vs 9,88 ± 3,56; p =0,010) compared to LN group respectively. NAS significantly decrease the expression of caspase-1 and degree of renal injury in mice models LN.

Keywords: Caspase-1, Degree Of Renal Injury, Lupus Nephritis, Pristane

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