Pengaruh Pemberian Pravastatin terhadap Kadar IFN-γ dan Il-10 pada Serum Tikus Wistar (Rattus norvegicus) Model Preeklamsi

Yanti, Entin Srihadi and Dr. dr. Bambang Rahardjo,, Sp.OG (K) and Dr. dr. Dwi Yuni Nur Hidayati,, M.Kes., Sp. MK (2021) Pengaruh Pemberian Pravastatin terhadap Kadar IFN-γ dan Il-10 pada Serum Tikus Wistar (Rattus norvegicus) Model Preeklamsi. Magister thesis, Universitas Brawijaya.

Abstract

Patofisiologi preeklamsi masih menjadi perdebatan, beberapa teori yang muncul menyebutkan bahwa preeklamsi berhubungan dengan kegagalan invasi trofoblas dan maladaptasi respon imun. Maladaptasi respon imun mengakibatkan ketidakseimbangan T helper cell (Th) tipe 1 dan 2 dalam upaya mempertahankan kehamilan. T helper (Th) berperan dalam mengatur sel imun dengan memproduksi sitokin tertentu, Th1 memproduksi sitokin inflamasi seperti Interferon (IFN-γ) sedangkan Th2 memproduksi sitokin antiinflamasi seperti IL-10. IFN-γ merupakan sitokin proinflamasi diketahui tinggi pada plasma ibu preeklamsi. Peningkatan level IFN-γ di plasenta menyebabkan perkembangan preeklamsi dengan mempengaruhi invasi trofoblas, remodelling arteri spiralis, apoptosis sel trofoblas, dan angiogenesis plasenta, serta dapat menurunkan regulasi IL-10. IL-10 memiliki fungsi perbaikan pembuluh darah berhubungan dengan relaksasi endotelin dan peningkatan ekspresi endotelin nitric oxcide syntase (eNOS). Pravastatin adalah obat anti hiperlipidemia golongan statin, inhibitor 3-hidroksi-3- metilglutaril (HMG-CoA) reduktase, sehingga mengurangi sintesis kolesterol intraseluler. Pravastatin meningkatkan Hmox-1, enzim yang berperan pada katabolisme CO. CO sebagai vasodilaor kuat dapat membantu menjaga keseimbangan angiogenik dengan menekan ekspresi sFLT-1 dan sENG serta meningkatkan TGF-β1 dan eNOS. Penelitian ini bertujuan untuk membuktikan pengaruh pravastatin terhadap penurunan kadar IFN-γ dan peningkatan kadar IL-10 pada serum tikus model preeklamsia. Jenis penelitian ini adalah eksperimental dengan pendekatan post test only control group design. Tikus betina 55 ekor dengan berat 150-200 gr dimattingkan selama 1x24 jam, diperiksa adanya vaginal plug dan kenaikan berat badan secara rutin hari pertama matting dan hari ke 8 post matting. Tikus bunting yang didapatkan sebanyak 27 ekor, 7 diantaranya terpaksa dikeluarkan dari penelitian karena termasuk dalam kondisi ekslusi dan drop out, tersisa 202 ekor tikus yg dibagi menjadi 5 kelompok perlakuan n=4. Kelompok kontrol negatif adalah tikus bunting normal diinjeksi PBS. Kelompok kontrol positif adalah tikus bunting yang mendapat injeksi L-NAME 125 mg/Kg/hari. Kelompok P1 adalah tikus bunting diinjeksi L-NAME 125 mg/Kg/hari + pravastatin 2 mg/hari. Kelompok P2 adalah tikus bunting diinjeksi L-NAME 125 mg/Kg/hari + pravastatin 4 mg/hari. Kelompok P3 adalah adalah tikus bunting diinjeksi L-NAME 125 mg/Kg/hari + pravastatin 8 mg/hari. Data dianalisis dengan bantuan SPSS 25 for windows. Uji normalitas menggunakan uji Saphiro-Wilk dengan p-value > 0.05 yang menunjukkan data terdistribusi normal. Hipotesis penelitian dibuktikan dengan uji One Way Annova pada kadar IFN-γ (p-value=0.000) dan kadar IL-10 (p-value=0.001). Hasil uji LSD menunjukkan perbedaan bermakna kadar IFN-γ (sig. 0.001) dan IL-10 (sig. 0.017) antara tikus bunting normal dan tikus bunting model preeklamsi. Perbedaan bermakna pada kadar IFN-γ didapatkan juga pada kontrol positif dengan setiap kelompok perlakuan P1 (sig. 0.003), P2 dan P3 (sig. 0.000), sedangkan kadar IL-10 menunjukkan perbedaan bermakna antara kontrol positif dengan kelompok P2 (sig. 0.045) dan kelompok P3 (sig. 0.001). Korelasi negatif kuat pengaruh dosis pravastatin terhadap kadar IFN-γ (p-value= 0.000;r=-0.876) dan korelasi negatif kuat pengaruh dosis pravasstatin terhadap IL-10 positif kuat pengaruh dosis pravastatin terhadap kadar IL-10 (p-value= 0.001;r=-0.822). Dengan demikian semakin tinggi dosis maka secara negatif menurunkan kadar IFN-γ dan secara positif meningkatkan kadar IL-10 pada tikus model preeklamsi. Kesimpulan dari penelitian ini yaitu pravastatin dapat menurunkan kadar IFN- γ dan meningkatkan kadar IL-10 pada tikus wistar model preeklamsia

English Abstract

The pathophysiology of preeclampsia is still being debated, several emerging theories suggest that preeclampsia is associated with failure of trophoblast invasion and maladaptation of the immune response. The maladaptation of the immune response results in an imbalance of T helper cells (Th) types 1 and 2 in an effort to maintain pregnancy. T helper (Th) plays a role in regulating immune cells by producing certain cytokines, Th1 produces inflammatory cytokines such as Interferon (IFN-γ) while Th2 produces anti-inflammatory cytokines such as IL-10. IFN-γ is a proinflammatory cytokine known to be high in the plasma of preeclamptic mothers. Elevated levels of IFN- in the placenta lead to the development of preeclampsia by influencing trophoblast invasion, spiral artery remodeling, trophoblast cell apoptosis, and placental angiogenesis, and may downregulate IL-10. IL-10 has a vascular repair function related to endothelin relaxation and increased expression of endothelin nitric oxide synthase (eNOS). Pravastatin is an anti-hyperlipidemic drug belonging to the statin class, a 3-hydroxy-3- methylglutaryl (HMG-CoA) reductase inhibitor, thereby reducing intracellular cholesterol synthesis. Pravastatin increases Hmox-1, an enzyme that plays a role in CO catabolism. CO as a strong vasodilator can help maintain angiogenic balance by suppressing the expression of sFLT-1 and sENG and increasing TGF-β1 and eNOS. Aims research to prove the effect of pravastatin on decreasing levels of IFN-γ and increasing levels of IL-10 in the serum of preeclampsia rat models. This type of research is experimental with a post test only control group design approach. In this study, 55 female wistar rats weighing 150-200 g were matted with male wistar rats for 1x24 hours, then separated and examined for vaginal plug and weight gain. Body weight checks were carried out routinely, before, after matting and on the 8th day post matting. There were 27 pregnant rats and only 20 that met the inclusion criteria. Pregnant rats were divided into 5 treatment groups n=4. The negative control group was normal pregnant rats injected with PBS. The positive control group was pregnant rats that received injection of L-NAME 125 mg/Kg/day. The P1 group were pregnant rats injected with L-NAME 125 mg/Kg/day and given pravastatin 2 mg/day per sonde. The P2 group were pregnant rats injected with LNAME 125 mg/Kg/day and given pravastatin 4 mg/day. The P3 group were pregnant rats injected with L-NAME 125 mg/Kg/day and given pravastatin 8 mg/day per sonde. The data were analyzed with the help of SPSS 25 for windows. The normality test used the Saphiro-Wilk test with p-value > 0.05 which indicates the data is normally distributed. The research hypothesis was proven by One Way Annova test on IFN-γ levels (pvalue=0.000) and IL-10 levels (p-value=0.001). LSD test showed a significant difference in levels of IFN-γ (sig. 0.001) and IL-10 (sig. 0.017) between normal pregnant rats and pregnant rats of preeclampsia model. Significant differences in IFN-γ levels were also found in positive controls with each treatment group P1 (sig. 0.003), P2 and P3 (sig. 0.000), while IL-10 levels showed significant differences between positive control and P2 group (sig. 0.045). ) and group P3 (sig. 0.001). Strong negative correlation of the effect of pravastatin dose on IFN-γ levels (p-value= 0.000; r=-0.876) and strong negative correlation of the effect of pravastatin dose on IL-10 and strong positive effect of pravastatin dose on IL-10 levels (p-value= 0.001 ;r=-0.822). Thus, based on the correlation test, it can be interpreted that the higher the dose, the lower the levels of IFN-γ negatively and positively increase the levels of IL- 10. The conclusion of this study is that pravastatin can reduce levels of IFN-γ and increase levels of IL-10 in preeclampsia model wistar rats

Item Type:	Thesis (Magister)
Identification Number:	042106
Subjects:	600 Technology (Applied sciences) > 618 Gynecology, obstetrics, pediatrics, geriatrics > 618.2 Obstetrics
Divisions:	S2/S3 > Magister Kebidanan, Fakultas Kedokteran
Depositing User:	soegeng sugeng
Date Deposited:	04 Jan 2022 01:24
Last Modified:	23 Feb 2022 01:49
URI:	http://repository.ub.ac.id/id/eprint/187763

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