Perbedaan Ekspresi mRNA BAX, mRNA BCL2, Rasio mRNA BAX/BCL2, dan Indeks Apoptosis Sel Trofoblas antara Preeklamsia Awitan Dini dan Awitan Lambat

MUHAMMAD JAVEDH IQBAL, Dr. dr. Diah Rumekti Hadiati, Sp.O.G, Subsp. K.Fm, M.Sc.; dr. Didik Setyo Heriyanto, Ph.D., Sp.P.A., Subsp. D.H.B.(K), Subsp. Kv.R.M.(K)

2023 | Tesis-Subspesialis | SUBSPESIALIS OBSTETRI DAN GINEKOLOGI

Latar Belakang: Preeklamsia awitan dini dan lambat memiliki karakteristik yang berbeda terkait tingkat stress oksidatif, apoptosis dan adaptasi mitokondria. Peningkatan stress oksidatif dapat menyebabkan aktivasi apoptosis jalur mitokondria. Penelitian ekspresi gen famili BCL2 terkait apoptosis pada sel trofoblas preeklamsia awitan dini dan lambat masih sedikit dan menunjukkan hasil yang inkonsisten. Tujuan: Menilai perbedaan ekspresi mRNA BAX, BCL2, rasio BAX/BCL2 dan indeks apoptosis antara preeklamsia awitan dini dan lambat, serta menilai korelasi antara mRNA BAX, BCL2, rasio BAX/BCL2 dengan indeks apoptosis. Metode Penelitian: Merupakan studi cross sectional dengan sampel FFPE plasenta pasien preeklamsia awitan dini dan lambat. Penilaian ekspresi mRNA BAX, BCL2 menggunakan pemeriksaan quantitative RT-PCR. Rasio BAX/BCL2 merupakan hasil pembagian ekspresi mRNA BAX dengan BCL2. Indeks Apoptosis dinilai dengan ekspresi fragmentasi DNA menggunakan metode Ligation-Mediated RT PCR. Hasil Penelitian: Rerata fold change mRNA BAX preeklamsia awitan dini lebih tinggi dibandingkan awitan lambat (6,02+-3,59 vs 2,82+-1,97; p=0,00). Rerata fold change mRNA BCL2 preeklamsia awitan dini tidak berbeda dengan awitan lambat (31,20+-17,94 vs 31,01+-27,60; p=0,98). Rasio fold change BAX/BCL2 preeklamsia awitan dini lebih tinggi dibandingkan awitan lambat (0,39+-0,78 vs 0,14+-0,13; p=0,01). Rerata cycle threshold (CT) fragmentasi DNA preeklamsia awitan dini lebih lebih rendah dibandingkan awitan lambat (28,07+-0,64 vs 30,63+-0,96; p=0,00). Terdapat korelasi negatif lemah antara fold change mRNA BAX dengan CT fragmentasi DNA (r=-0,30; p=0,02). Kesimpulan: Ekspresi relatif mRNA BAX, rasio BAX/BCL2 dan indeks apoptosis sel trofoblas pada preeklamsia awitan dini lebih tinggi dibandingkan awitan lambat. Walaupun memiliki korelasi positif lemah, mRNA BAX lebih berperan dalam apoptosis plasenta preeklamsia dibandingkan mRNA BCL2.

Background: Early-onset and late-onset preeclampsia have different characteristics related to oxidative stress and mitochondrial adaptation levels. Increased oxidative  stress  can  activate  the  mitochondrial  pathway  apoptosis. Research on apoptosis-related BCL2 family gene expression in trophoblast cells between early-onset and late-onset preeclampsia still shows inconsistent results. bjectives: Assess the differences in expression of BAX, BCL2 mRNA, BAX/BCL2 ratio, and apoptosis index between early-onset and late-onset preeclampsia, and assess the correlation between BAX, BCL2 mRNA, BAX/BCL2 ratio and apoptosis index of the trophoblastic cell in preeclampsia. Methods: Cross-sectional study using FFPE placenta samples of early-onset and late-onset preeclampsia. Assessment of BAX, BCL2 mRNA expression using quantitative RT-PCR method. BAX/BCL2 ratio was obtained from the division between BAX and BCL2 mRNA expression. The apoptosis index was assessed by examination of DNA fragmentation expression using the ligation-mediated RT- PCR method. Results: Early-onset has a higher mean fold change in BAX mRNA than late-onset preeclampsia (6.02+-3.59 vs 2.82+-1.97; p=0.00). The mean fold change of BCL2 mRNA was not significantly different between early-onset and late-onset preeclampsia (31.20+-17.94 vs 31.01+-27.60; p=0.98). The mean BAX/BCL2 fold change ratio of the early-onset preeclampsia was higher than that of the late-onset group (0.39+-0.78 vs 0.14+-0.13; p=0.01). Early-onset preeclampsia had lower mean cycle threshold (CT) DNA fragmentation than late-onset preeclampsia (28.07+-0.64 vs 30.63+-0.96; p=0.00). There was a modest negative correlation between fold change mRNA BAX and CT DNA fragmentation (r=-0.30; p=0.02). Conclusions: The relative expression of BAX mRNA, ratio BAX/BCL2, and apoptosis index of trophoblastic cells in early-onset are higher than in late-onset preeclampsia. The relative expression of BAX mRNA plays a more significant function in the placental apoptotic pathway of the patient with preeclampsia, despite a modest positive association.

Kata Kunci : mRNA, BAX, BCL2, Apoptosis, Preeklamsia, Preeclampsia