Gebe sıçanlara bevacizumab uygulayarak preeklampsi çalışmalarında kullanılabilecek deneysel hayvan modeli oluşturulabilir.

GİRİŞ ve AMAÇ: Bir anjiogenez inhibitörü olan bevacizumab uygulayarak sıçanlarda preeklampsi modeli oluşturmak. YÖNTEM ve GEREÇLER: Toplam 16 gebe sıçana intraperitoneal 10 mg/kg bevacizumab ya da 0.1 cc serum fizyolojik 4 ve 8. günlerde uygulandı. Sıçanların kan basınçları, ağırlıkları ve proteinüri miktarları 0 ve 20. günlerde değerlendirildi. 20. günde sıçanlardan kan örnekleri alınarak vasküler endotelyal büyüme faktörü (VEGF) ve çözülebilir Fms benzeri protein kinaz (SFlt-1) seviyeleri ölçüldü. Aynı gün ötenazi uygulanılarak plasenta ve yavruların ağırlıkları değerlendirildi. Immünohistokimyasal olarak anjiogenez belirteçleri ve mikro damar yoğunluğu incelendi. BULGULAR: Bevacizumab uygulanan grupta daha düşük VEGF (p = 0.038) ve daha yüksek SFlt-1 (p = 0.015) seviyeleri saptandı. Benzer şekilde bevacizumab uygulanan sıçanların sistolik (p=0.050) ve diastolik (p=0.046) kan basınçları daha yüksek bulundu. Bevacizumab uygulanan sıçanlarda 20. günde proteinüri miktarları 0. güne göre belirgin olarak daha yüksekti (p=0.026). Her ne kadar daha yüksek AST, ALT, BUN, kreatinin, böbrek glomerüler endotelyosis skorları ile daha düşük plasental VEGF ve mikro damar yoğunluğu gözlenmiş olsa da, istatistiksel olarak anlamlı fark saptanmadı (p>0.05). TARTIŞMA ve SONUÇ: Çalışmamızda gebe sıçanlara bevacizumab uygulayarak preeklampsi modeli oluşturulabileceğine dair olumlu sonuçlar elde edilmiştir.

Anahtar Kelimeler:

bevacizumab, preeklampsi, sıçan modeli

Bevacizumab-treated pregnant rats may constitute an experimental model for studying preeclampsia.

INTRODUCTION: To develop a rat model of preeclampsia by administering bevacizumab, an angiogenesis inhibitor. METHODS: Sixteen pregnant rats were randomly allocated to intraperitoneal injection of 10 mg/kg bevacizumab or 0.1 cc intraperitoneal serum physiologic on the 4th and 8th days of gestation. Blood pressure, body weight, and proteinuria were measured on both day 0 (D0) and day 20 (D20). Blood samples were collected on D20 for analysis, including for determining vascular endothelial growth factor (VEGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1) levels. On the same day, the mice were euthanized, the placentas and pups were weighted, and the angiogenesis markers and microvessel density were evaluated using immunohistochemical methods. RESULTS: Lower serum VEGF (p = 0.038) and higher SFlt-1 (p = 0.015) levels were observed in bevacizumab-treated pregnant rats. Bevacizumab-treated pregnant rats had significantly higher systolic (p = 0.050) and diastolic (p = 0.046) blood pressures compared to the controls. Additionally, the bevacizumab group showed a significant increase in proteinuria on D20 compared to that on D0 (p = 0.026). Although higher serum AST, ALT, BUN, and creatinine levels and renal glomerular endotheliosis scores as well as lower placental VEGF and microvessel density were noted in bevacizumab-treated rats, these differences were not statistically significant (p > 0.05 for each). DISCUSSION AND CONCLUSION: The promising results of this trial show that bevacizumab treatment in pregnant rats might provide a model to study human preeclampsia

Keywords:

bevacizumab, preeclampsia, rat model,

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