Pengaruh Pemberian Ekstrak Buah Delima Merah (Punica Granatum) Terhadap Kadar Soluble Fms Like Tyrosine Kinase 1 (Sflt-1) Dan Soluble Endoglin (Seng) Pada Kultur Huvecs Yang Dipapar Plasma Penderita P

Fatmawati (2015) Pengaruh Pemberian Ekstrak Buah Delima Merah (Punica Granatum) Terhadap Kadar Soluble Fms Like Tyrosine Kinase 1 (Sflt-1) Dan Soluble Endoglin (Seng) Pada Kultur Huvecs Yang Dipapar Plasma Penderita P. Magister thesis, Universitas Brawijaya.

Abstract

Preeklampsia merupakan sindrom spesifik dalam kehamilan dan patofisiologi preeklampsia sampai saat ini masih belum jelas sehingga dikenal sebagai “ disease of ory “ . Preeklampsia berkaitan dengan morbiditas serta mortalitas ibu dan janin. Jalur molekuler mengatur proses vaskulogenesis dan angiogenesis membutuhkan faktor angiogenik dan anti angiogenik yang bekerjasama dalam perkembangan plasenta. Adanya Invasi trofoblas dan remodeling yang tidak adekuat pada arteri spiralis menyebabkan terjadinya penurunan perfusi plasenta atau iskemia plasenta sehingga mengakibatkan peningkatan reactive oxygen species (ROS) yaitu anion superoksida (O2 -), hidrogen peroksida (H2O2), radikal hidroksi (OH-) dan peroksinitrit (ONOO-) yang menyebabkan penurunan tingkat oksidan dalam mengikat radikal bebas sehingga terjadi stres oksidatif.Pada preeklampsia adanya invasi dan remodelling yang tidak adekuat mengakibatkan terjadi ketidakseimbangan antara peningkatan faktor anti angiogenik yaitu sFlt-1 dan sEng. Stres oksidatif dapat dicegah dengan pemberian antioksidan. dengan pemberian antioksidan dapat menurunkan faktor sFlt-1 dan sEng dengan menghalangi p38 MAPK, NF-kB dan ekspresi heme oxygenase (HO-1)/CO. Upaya meningkatkan status antioksidan dalam tubuh dilakukan dengan mengkonsumsi zat–zat gizi yang mengandung antioksidan. Antioksidan ini paling banyak didapatkan dari buah–buahan terutama buah delima ( Punica granatum ). Pemberian supplementasi antioksidan dapat mengurangi insiden terjadinya preeklampsia terutama konsentrasi dari sFlt-1 dan sEng. Tujuan Penelitian ini adalah Untuk membuktikan pemberian ekstrak buah delima merah ( Punica granatum ) terhadap penurunan kadar sFlt-1 dan sEng pada kultur HUVECs yang dipapar plasma penderita preeklampsia. Metode penelitian ini adalah true experimental (eksperimental sesungguhnya) dengan pendekatan post test only control group design. sampel dari penelitian ini adalah sel endotel yang berasal dari tali pusat bayi baru lahir (BBL), yang berasal dari ibu bersalin dengan cara Sectio Caesaria (SC) tanpa komplikasi, plasma kehamilan normal dan plasma penderita preeklampsia. Jumlah replikasi pada penelitian ini adalah 5 replikasi dengan 1 kelompok kontrol negatif, 1 kelompok kontrol positif dan 3 kelompok dengan perlakuan dengan pemberian ekstrak buah delima merah ( Punica granatum ) yaitu pemberian dosis 14 ppm, 28 ppm ,dan 56 ppm dengan masa inkubasi 24 jam. Kadar sFlt-1 dan sEng diukur dengan menggunakan enzyme-linked immunosorbent assay (ELISA). Analisa statistik menggunakan uji t sampel bebas, uji Anova One Way uji perbandingan berganda ( Multiple Comparisons ) dengan uji Beda Nyata Terkecil/BNT ( Least Significant Difference/LSD ), dan dilanjutkan uji korelasi Pearson. Berdasarkan hasil statistik kadar sFlt-1 pada kontrol positif (61.70±5.48 ng/dL) lebih tinggi dari kontrol negatif (4.40±0.42 ng/dL) dan kadar sEng pada kontrol positif (7411±806.8 pg/dL) lebih tinggi dari kontrol negatif (1801.3±199.9 pg/dL). Berdasarkan uji hasil Anova One Way diperoleh ada perbedaan yang bermakna rerata kadar sFlt-1 dan sEng keempat kelompok sampel pengamatan, hal ini ditunjukkan dengan nilai p-value = 0.000 kemudian dilanjutkan dengan uji perbandingan berganda ( Multiple Comparisons ) dengan uji Beda Nyata Terkecil/BNT ( Least Significant Difference/LSD ) ada perbedaan yang bermakna rerata kadar sFlt-1 dan sEng antara kelompok kontrol positif dengan kelompok perlakuan pemberian ekstrak delima merah ( Punica granatum) dosis 14 ppm , 28 ppm dan 56 ppm. Pada kadar sFlt-1 diperoleh hasil kontrol positif (61.70±5.48a ng/dL), kelompok perlakuan pemberian ekstrak delima merah 14 ppm (18.39±1.72b ng/dL), pemberian ekstrak delima merah 28 ppm (17.47±0.68b ng/dL), dan pemberian ekstrak delima merah 56 ppm (5.64±1.33c ng/dL). Sedangkan pada kadar sEng diperoleh hasil kelompok kontrol positif (7411±806.8a pg/dL), kelompok perlakuan pemberian ekstrak delima merah 14 ppm (6352.7±290.5b pg/dL), pemberian ekstrak delima merah 28 ppm (4796±726.1c pg/dL) dan pemberian ekstrak delima merah 56 ppm (2467±809.7d pg/dL). Hal ini menunjukkan bahwa perlakuan pemberian ekstrak delima merah berbagai dosis berpengaruh bermakna terhadap penurunan kadar sEng pada kultur HUVECs preeklampsia. Berdasarkan hasil analisis data dari uji korelasi Pearson antara kadar sFlt-1 dengan kadar sEng pada sampel kultur HUVECs preeklampsia yang diberi ekstrak delima merah ( Punica granatum) ada hubungan yang bermakna antara kadar sFlt-1 dengan kadar sEng ( p-value =0.000 ) pada kultur HUVECs yang dipapar dengan plasma penderita preeklampsia dan perlakuan pemberian ekstrak delima merah dosis 14 ppm, 28 ppm, dan 56 ppm dengan nilai koefisien korelasi yang tinggi yaitu 0.893. Sedangkan pada hasil uji korelasi perlakuan dosis ekstrak buah delima merah dengan kadar sFlt1 dan kadar sEng menunjukkan bahwa ada hubungan yang bermakna antara dosis dengan kadar sFlt1 dan sEng dengan nilai koefisien korelasi yaitu r = -0.832. Hal ini menunjukkan bila terjadi peningkatan dosis ekstrak buah delima merah maka akan terjadi penurunan kadar sFlt-1 dan sEng Simpulan dari penelitian ini adalah pemberian ekstrak buah delima merah ( Punica granatum ) dengan dosis 14 ppm, 28 ppm dan 56 ppm menurunkan kadar sFlt-1 dan sEng pada kultur HUVECs yang dipapar plasma penderita preeklampsia

English Abstract

Preeclampsia is a specific syndrome in pregnancy and pathophysiology of preeclampsia is still vague and refore it is well-known as "disease of ory". Preeclampsia is associated with morbidity and mortality of mo r and fetus. Molecular pathways regulated vaskulogenesis process, and angiogenesis required angiogenic and anti-angiogenic factors that cooperated in development of placenta. presence of trophoblast invasion and inadequate remodelling in spiral arteries caused decrease of placental perfusion or placenta ischemia. This, increased reactive oxygen species (ROS) which were superoxide anion (O2 -), hydrogen peroxide (H2O2), hydroxyl radical (OH-) and peroxynitrite (ONOO-), which decreased level of oxidants to scavenge free radicals. This phenomenon caused -so-called oxidative stress. In preeclampsia, presence of inadequate invasion and remodeling, resulted an imbalance in increase of anti-angiogenic factors which were sFlt-1 and sEng . Oxidative stress could be prevented by antioxidants. Consuming antioxidants could decrease sFlt-1 and sEng factors by blocking p38 MAPK, NF-kB and heme oxygenase (HO-1)/CO expression . Improving antioxidant status in body could be done by consuming nutrients that contain antioxidants. se antioxidants could be obtained mostly from fruits especially pomegranate ( Punica granatum ). Provision of antioxidant supplementation may reduce incidence of preeclampsia, especially concentration of sFlt-1 and sEng. purpose of this study was to prove that provision of red pomegranate fruit extract ( Punica granatum ) could decrease levels of sFlt-1 and sEng in HUVECs culture which is exposed by Preeclampsia Patients` Plasma. method of this research was True Experimental ( real experimental ) by using Post Test Only Control Group Design approach. samples of this research were endo lial cells derived from umbilical cord of newborns (BBL) from an uncomplicated Sectio-Caesaria(SC)-mo r, normal pregnancy plasma and plasma preeclampsia. replication number of this research was 5, which belongs to 1 negative control group, 1 positive control group, and 3 experimental groups treated with extract of red pomegranate ( Punica granatum ) with dose of 14 ppm, 28 ppm, and 56 ppm with a 24-hour incubation period. levels of sFlt-1 and sEng were measured by using Enzyme-Linked Immunosorbent Assay (ELISA). Statistical analyses which were used in this research were independent samples t-test, One Way ANOVA multiple comparison tests with Least Significant Difference / LSD, and Pearson correlation test. Based on statistical results, levels of sFlt-1 of positive controls (which is 61.70 ± 5.48 ng/dL) was higher than negative control (4.40 ± 0.42 ng/dL), and sEng levels in positive control (7411 ± 806.8 pg/dL) was also higher than negative control (1801.3 ± 199.9 pg/dL). Based One Way ANOVA test, it could be seen that re was a different mean levels of sFlt-1 and sEng of fourth observed sample groups. difference was shown by p-value = 0.000 _. When test was followed by ano r test which was Multiple Comparisons test with Least Significant Difference test / LSD, result showed that re were significant differences of mean levels of sFlt-1 and sEng between positive control group with experimental group extract of red pomegranate (Punica granatum) dose of 14 ppm, 28 ppm and 56 ppm. At levels of sFlt-1, it was obtained that positive control is 61.70±5.48a ng/dL, experimental group red pomegranate extract with dose 14 ppm was18.39±1.72b ng/dL, experimental group red pomegranate extract with dose 28 ppm is 17.47±0.68b ng/dL, and experimental group red pomegranate extract with dose 56 ppm was 5.64±1.33c ng/dL. For levels of sEng, it was obtained that score of positive results of control group was 7411±806.8a pg/dL, experimental group red pomegranate extract with dose 14 ppm is 6352.7±290.5b pg/dL, experimental group red pomegranate extract with dose 28 ppm is 4796±726.1c pg/dL and experimental group red pomegranate extract with dose 56 ppm is 2467±809.7d pg/dL. This showed that treatment of various doses of red pomegranate extract gave meaningful effect of decrease of sEng levels in HUVECs preeclampsia culture. data analysis of Pearson correlation test of levels of sFlt-1 and levels of sEng in HUVECs culture which was exposed by Preeclampsia Patients` Plasma which were given extracts of red pomegranate ( Punica granatum ), showed significant correlation between levels of sFlt-1 and levels of sEng (p-value = 0.000 _ ) in preeclampsia HUVECs culture samples and red pomegranate extract treatment with dose of 14 ppm, 28 ppm, and 56 ppm, with a high correlation coefficient value which is 0893. While results of correlation test dose treatment with a red pomegranate fruit extract sFlt1 levels and sEng levels indicate that re was a significant relationship between dose levels of sFlt1 and sEng with correlation coefficient which is r = -0832. This showed that “if re is an increase in dose of red pomegranate fruit extract, re will be a decrease in levels of sFlt-1 and sEng” conclusions of this research showed that red pomegranate fruit extract ( Punica granatum ) with dose of 14 ppm, 28 ppm and 56 ppm could decrease levels of sFlt-1 and sEng in HUVECs culture which was exposed by Preeclampsia Patients` Plasma

Item Type: Thesis (Magister)
Identification Number: TES/615.323 76/FAT/p/2015/041503356
Subjects: 600 Technology (Applied sciences) > 615 Pharmacology and therapeutics > 615.3 Organics drugs
Divisions: S2/S3 > Magister Kebidanan, Fakultas Kedokteran
Depositing User: Sugiantoro
Date Deposited: 07 Aug 2015 14:41
Last Modified: 07 Aug 2015 14:41
URI: http://repository.ub.ac.id/id/eprint/158088
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