Background and purpose:
Our previous work has proved that Intracerebral hemorrhage (ICH) induces angiogenesis, accompanied by upregulation of vascular endothelial growth factor (VEGF) and its receptors. As the most potent mitogen of endothelial cells (ECs), VEGF must bind to its receptor_vascular endothelial growth factor receptor-2, to make it be phosphorylated, which plays the roles in promoting proliferation, migration, survival of ECs. In this study, our purpose is to investigate the effect of VEGF receptor inhibition on angiogenesis after ICH.
Method:
Fifteen Kunming mice were randomly divided into 3 groups, including sham control (n=5), ICH group (n=5), and SU5416-treated group (n=5). ICH model was induced by injection collagenase type VII into right globus pallidus stereotaxically. SU5416-treated group was injected by SU5416 (10 mg/kg per dose) intraperitoneally after ICH induction. Intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) was used to label new-born ECs. Neurological severity score (NSS), corner turn test and foot-fault test were used to investigate the neurological function at 1d, 3d and 7d following the surgery. Angiogenesis and the level of p-VEGFR-2 were evaluated at 7d by immunohistochemistry.
Results:
At 1d, there is no difference between the two ICH-induced groups in NSS, corner turn test, foot-fault test; at 3d and 7d, the NSS in ICH group is significantly lower than that of SU5416-treated group (
P
<0.05), and the times for right-turn and foot-fault in ICH group are notably fewer than those of SU5416-treated group (
P
<0.05). At 7d, no expression of p-VEGFR-2 was detected in sham control animals, while the expression of p-VEGFR-2 in ICH group is notably higher than that in SU5416-treated group (
P
<0.05); and the expression of p-VEGFR-2 is located in vWF-immunoreactive ECs; there is no BrdU-labeled nuclear in vessels observed in sham-control mice, but BrdU-labeled nuclei in vessels in ICH group are remarkably more than those in SU5416-treated group (
P
<0.05).
Conclusions:
Activation of VEGFR-2 is an important mechanism for angiogenesis after ICH, which is related with the recovery of neurological behavioral function.
Buyang huanwu decoction promotes angiogenesis via vascular endothelial growth factor receptor-2 activation through the PI3K/Akt pathway in a mouse model of intracerebral hemorrhage
