Taufiq Hidayat, dr., SpA (2018) PERAN MMP-1 TIMP-1 RASIO MMP-1 TIMP-1 DAN KOLAGEN-1 PADA HAMBATAN FIBROSIS OTOT JANTUNG VENTRIKEL KANAN HEWAN COBA MODEL HIPERTENSI ARTERI PULMONAL YANG MENDAPAT EKSTRAK BUAH DELIMA (PUNICA GRANATUM L). Thesis thesis, Universitas Airlangga.

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Abstract

Background: Pulmonary arterial hypertension (PAH) is defined as the mean pulmonary artery pressure (pPA) at rest over 25 mmHg which may cause myocardial fibrosis. The process involves collagenase, the metalloproteinase matrix (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) that affect the balance of type I collagen synthesis and degradation. The accumulation of type I collagen in right ventricular heart muscle can result in right ventricular fibrosis. Pomegranate extracts contain active ellagic acid ingredients that have anti-inflammatory, anti-proliferative, antioxidant, and ACE inhibitory effects on tissue fibrosis with no side effects. However, until now there has been no research on the mechanism of the effects of pomegranate on the right ventricular myocardial fibrosis process due to the emergence of PAH caused by congenital heart disease with left to right shunting. Objective: To evaluate the effectiveness of pomegranate extract on fibrosis process due to HAP especially on right ventricular myocardium by observing at the number of cells expressing MMP-1, TIMP-1, MMP-1 / TIMP-1 ratio and collagen 1 on right ventricular heart muscle of hypertension pulmonary artery model mice . Method: This research is a laboratory experimental research conducted on white mice (Rattus norvegicus) strain Sprague Dawley male 3 month old with body weight 300-500 gram in laboratory of Biochemistry Faculty of Medicine University of Airlangga. Model mice were grouped as control and experimental groups who received CMC for 2 weeks and 4 weeks. Monocrotaline is injected to mice to induce pulmonary arterial hypertension. This research material using pomegranate extract from all parts of pomegranate (Punica granatum L) in powder form and has been standardized containing 40% ellagic acid produced by Xi'an Biof Bio-Technology Co., Ltd. (Room 1-1111, High-tech Venture Park, No. 69 Jinye Road, Gaoxin Distric of Xi'an, People Republic of China). As a comparison, this study uses a solution of sodium carboxymethyl cellulose (CMC) 0.3%. Results: The mean systolic and pulmonary artery systolic pressure in the pomegranate extract model was lower than the control group and significantly different in the observation after 2 weeks and 4 weeks (p = 0,002). MMP-1 expression of right ventricular heart muscle in the control group was less than pomegranate extract after 2 weeks or 4 weeks (p <0.001 and p <0.001). The number of cells expressed in TIMP-1 was more in the control group than the observed EBD for 2 weeks and 4 weeks (p <0.001). The ratio of cell numbers expressing MMP-1 / TIMP-1 was higher in the pomegranate extract group than in controls and differed significantly in observations after 2 weeks or 4 weeks (p <0.001). The number of cells expressing type I collagen in the pomegranate extract group was lower than the control on observation after 4 weeks (p <0.001).

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