Suppression of Angiotensin-(1–7) on the Disruption of Blood-Brain Barrier in Rat of Brain Glioma

[摘要] Glioblastoma multiforme (GBM) is the most primary brain tumor, specially characterized with the damage of blood-brain barrier (BBB). The Ang-(1–7) was proven to have an inhibitory effect on glioblastoma growth. However, its role on blood–brain barrier (BBB) and the underlying molecular mechanism remains unclear. In this study, Ang-(1–7) significantly relieved the damage of blood-brain barrier in rats with intracranial U87 gliomas as evaluated by magnetic resonance imaging (MRI). Furthermore, its treatment attenuated BBB permeability, tumor growth and edema formation. Similarly, Ang-(1–7) also decreased U87 glioma cells barrier permeability in vitro. Further analysis showed that Ang-(1–7) could effectively restore tight junction protein (claudin-5 and ZO-1) expression levels both in rats and U87 glioma cells by affecting the activation of JNK pathway. SP600125, an inhibitor of JNK, significantly enhanced the expression of Claudin-5 and ZO-1, and decreased the disruption of BBB and enhanced the efficiency of Ang-(1–7) in glioma rats. Taken together, this study demonstrated a protective role of Ang-(1–7) in glioma-induced blood-brain barrier damage by regulating tight junction protein expression. Accordingly, Ang-(1–7) may become a promising therapeutic agent against glioma.

[关键词] Ang-(1–7);Glioma;Blood–brain barrier;Claudin-5;ZO-1