Razzaqy, NIM011518016304 (2019) PENGARUH METFORMIN TERHADAP EKSPRESI TUMOR NECROTIZING FACTOR-α, ENZIM MATRIX METALLOPROTEINASE-3, DAN TISSUE INHIBITOR OF MATRIX METALLOPROTEINASE-1 PADA MODEL FIBROSIS KAPSUL LENSA IN VITRO (Studi Eksperimental Laboratorium). Thesis thesis, Universitas Airlangga.

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Abstract

Purpose: to investigate metformin influence on the expression of TNF-α, MMP-3, and TIMP-1 in lens capsule fibrosis model from cultured HLEC. Methods: HLECs were isolated from anterior capsule collected from adult cataract patient. Cultured cells were divided into control FBS 10% group and treatment groups of various doses of metformin, i.e. 0.1 mM, 0.5 mM, and 1.0 mM. TNF-α was determined using human TNF-α ELISA kit. Immunoabsorbances were read at optical density of 450 nm. Expressions of MMP-3 and TIMP-1 were determined utilizing antibody FITC immunostainig and the results were observed under fluorescence microscope. Oneway ANOVA followed by Tukey HSD posthoc test with significant level of p<0.05 was used in statistical analysis. Results: Low concentration of TNF-α was detected in all groups, with the lowest expression was found in FBS 10% group (5.9896 pg/mL ± 0.0357 pg/mL). This study exhibited that MMP-3 expression decreases after administration of metformin 0.1 mM (3.0102 x 105 pixels ± 2.0813 x 105 pixels), 0.5 mM (2.5817 x 105 pixels ± 1.0759 x 105 pixels), and 1.0 mM (1.8069 x 105 pixels ± 1.2715 x 105 pixels) with significant reduction of MMP-3 expression in 1.0 mM concentration compared to control group (p=0.012). TIMP-1 staining lessens after treatment of 0.1 mM (6.3759 x 105 pixels ± 3.3324 x 105 pixels), 0.5 mM (2.6662 x 105 pixels ± 1.6261 x 105 pixels), and 1.0 mM (3.2540 x 105 pixels ± 1.6244 x 105 pixels) metformin with statistically significant decrease in 0.5 mM (p=0.003) and 1.0 mM (p=0.008) metformin group compared to FBS 10% group. Conclusions: Metformin might have antifibrotic effect on HLEC in proliferative phase of wound healing by inhibiting MMP-3 and TIMP-1 regardless of TNF-α level.

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