Ramadhani, Nofi Nurina and Prof.Dr.dr.Loeki Enggar Fitri, Sp.ParK. and dr. Eviana Norahmawati, SpPA(K). (2019) Ekspresi Nuclear Factor Kappa B (NF-κB) dan Peroxisome Proliferator Activated Receptor-γ (PPAR-γ) Pada Jaringan Plasenta Mencit Terinfeksi Plasmodium berghei Serta Korelasinya Dengan Derajat Parasitemia dan Berat Badan Janin. Magister thesis, Universitas Brawijaya.
Abstract
Infeksi malaria pada kehamilan merupakan salah satu penyebab kematian ibu dan tingginya angka berat badan lahir rendah pada janin. Keberadaan parasit pada ibu hamil yang terinfeksi malaria akan menyebabkan akumulasi atau sekuestrasi eritrosit terinfeksi di daerah intervili plasenta. Proses ini yang dikenal sebagai malaria plasenta. Selama malaria plasenta berlangsung, terjadi infiltrasi sel inflamasi dan peningkatan sitokin proinflamasi di daerah intervilous. Meskipun telah diketahui bahwa eritrosit terinfeksi dan akumulasi sitokin maupun kemokin pada plasenta dapat menghasilkan kehamilan yang merugikan, namun mekanisme dalam menyebabkan kerusakan pada jaringan plasenta belum banyak dieksplorasi lebih lanjut. Salah satu faktor yang mempengaruhi tingkat kerusakan jaringan plasenta adalah aktivasi NFκB yang berperan dalam proses pro-inflamasi, serta PPAR-ɣ sebagai salah satu faktor yang meregulasi anti-inflamasi. Adanya gangguan atau kerusakan akibat proses inflamasi pada jaringan plasenta khususnya sel trofoblas berpotensi menyebabkan terganggunya proses transport nutrisi maternal ke janin. Dengan demikian, tujuan penelitian ini adalah untuk mengetahui patofisiologi malaria plasenta ditinjau dari dua jalur yang diduga turut berperan yakni jalur NF-κB dan PPAR-ɣ dan korelasinya terhadap derajat parasitemia serta berat badan janin. Penelitian ini dilakukan secara in vivo, yakni menggunakan Plasmodium berghei yang diinokulasikan pada mencit. Metode penelitian yang digunakan adalah “True Experimental Design” dengan desain “Randomized Posttest Only Controlled Group”. Sampel yang digunakan adalah hewan coba mencit galur balb/c bunting (primigravida) yang dibagi menjadi kelompok perlakuan yang diinfeksi Plasmodium berghei pada hari ke-9 pasca kawin (9 mencit) dan kelompok kontrol yang tidak diinfeksi Plasmodium berghei (8 mencit). Pembedahan dilakukan pada hari ke-18 pasca kawin untuk mengisolasi janin dan plasenta. Peningkatan ekspresi NFκB dan PPAR-ɣ sel trofoblas pada plasenta dihitung dengan pewarnaan immunohistokimia (Allred score), pemeriksaan derajat parasitemia diamati melalui hapusan darah tepi pada saat sebelum pembedahan dengan menggunakan pewarnaan giemsa dan diamati dengan mikroskop perbesaran 1000x, sementara berat badan janin diukur dengan skala analitikal (Mettler AE 50). Hasil analisis Mann Whitney menunjukkan bahwa terdapat perbedaan signifikan pada ekspresi NF-κB dan PPAR-ɣ antara kelompok kontrol dan perlakuan (p=0,0001; p=0,012). Analisis berat badan dengan menggunakan Mann Whitney juga menunjukkan hasil yang berbeda signifikan (p=0,003). Sementara, pada uji korelasi Pearson tidak diperoleh adanya hubungan antara NF-κB terhadap derajat parasitemia (r = 0,-576; p= 0,175) , serta NF-κB terhadap berat badan janin (r = -0,177; p=0,705). Selain itu, uji korelasi Pearson juga menunjukkan tidak diperoleh hubungan antara PPAR-γ dengan derajat parasitemia (r = 0.-579; p=0,173) maupun terhadap berat badan janin (r=0,653, p=0,111). Dengan demikian, dapat disimpulkan bahwa terdapat perbedaan yang bermakna pada ekspresi NF-κB dan PPAR-ɣ sel trofoblas plasenta yang diinduksi malaria. Namun, tidak ditemukan adanya korelasi ekspresi NF-κB dan PPAR-ɣ terhadap derajat parasitemia maupun berat badan janin.
English Abstract
Malaria infection in pregnancy is one of the causes of maternal death and high rates of low birth weight in the fetus. The presence of parasites in pregnant women infected with malaria will cause accumulation or sequestration of infected erythrocytes in the placental intervillous region. This process is known as placental malaria. As long as placental malaria takes place, inflammatory cell infiltration takes place and increases in proinflammatory cytokines in the intervillous region. Although it is well known that erythrocytes are infected and the accumulation of cytokines and chemokines in the placenta can produce adverse pregnancies, the mechanism for causing damage to placental tissue has not been explored much. One of the factors that affect the level of damage to placental tissue is the activation of NFκB which plays a role in the pro- inflammatory process, as well as PPAR-ɣ as one of the anti-inflammatory regulating factors. The presence of damage due to the inflammatory process in placental tissue, especially in trophoblast cells has the potential to cause disruption of the process of maternal nutrition transport to the fetus. Thus, the purpose of this study was to determine the pathophysiology of placental malaria in terms of two factors that were thought to contribute, namely the NF-κB and PPAR-ɣ as well as their correlation with the degree of parasitemia and fetal weight. This research was conducted in vivo, using Plasmodium berghei which was inoculated in mice. The research method used is "True Experimental Design" with the design of "Randomized Posttest Only Controlled Group". The sample used was balb / c pregnant (primigravida) mice which were divided into treatment groups infected with Plasmodium berghei on the 9th day after mating (9 mice) and the control group which weren’t infected with Plasmodium berghei (8 mice). Surgery is performed on the 18 th day after mating, to isolate the fetus and placenta. Increased expression of NF-κB and PPAR- of trophoblast cells in the placenta was processed by immunohistochemical staining (counting method using Allred score), examination of the degree of parasitemia was observed through peripheral blood smear before surgery using giemsa staining and a microscope with 1000x magnification, while fetal weight was measured by scale analytical (Mettler AE 50). The Mann Whitney analysis results showed that there were significant differences in NF-κB and PPAR-ɣ expression between the control and treatment groups (p = 0,0001; p = 0.012). Analysis of body weight using Mann Whitney also showed significant difference (p = 0.003). Meanwhile, in the Pearson correlation test there was no relationship found between NF-κB to the degree of parasitemia (r = 0, -576; p = 0.175), and NF-κB to fetal weight (r = -0.177; p = 0.705). In addition, the Pearson correlation test also showed no relationship between PPAR-γ and the degree of parasitemia (r = 0.- 579; p = 0.173) and fetal weight (r = 0.653, p = 0.111). Thus, it can be concluded that there are significant differences in the expression of NF-κB and PPAR-ɣ malaria-induced placental trophoblast cells. However, no correlation was found between NF-κB and PPAR-ekspresi expression to the degree of parasitemia or fetal weight.
Other obstract
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| Item Type: | Thesis (Magister) |
|---|---|
| Identification Number: | TES/618.3/RAM/e/2019/041901552 |
| Subjects: | 600 Technology (Applied sciences) > 618 Gynecology, obstetrics, pediatrics, geriatrics > 618.3 Diseases and complications of pregnancy |
| Divisions: | S2/S3 > Magister Ilmu Biomedis, Fakultas Kedokteran |
| Depositing User: | yulia Chasanah |
| Date Deposited: | 06 Sep 2022 02:54 |
| Last Modified: | 06 Sep 2022 02:55 |
| URI: | http://repository.ub.ac.id/id/eprint/193973 |
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