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

Year 2018, , 301 - 308, 28.09.2018

Abdullah Boztosun Şafak Ongan , Hatice Özer Remzi Atilgan Şehmus Pala

https://doi.org/10.31362/patd.451705

Abstract

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. 

Keywords

bevacizumab, preeklampsi, sıçan modeli

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

Abstract

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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