[Effects of the transplantation of adipose-derived stem cell on the expression of Notch1-Dll4 signaling pathway in brain of rats with focal cerebral ischemia].
OBJECTIVE
To investigate the effects of the transplantation of adipose-derived stem cells (ADSC) on the expression of Notch1-Dll4 signaling pathway in brains of rats with focal cerebral ischemia.


METHODS
Sixty-five male adult Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, MCAO (occlusion of middle cerebral artery) group, ADSC-treated group and ADSC & DAPT-treated group. A permanent model of focal cerebral ischemia was established by modified Zea-Longa's method. At 24 hours post-MCAO, 1×10(6) DAPT-labeled ADSC were injected into the lateral ventricle of rats in the ADSC-treated group and the same dose of ADSC with DAPT (γ secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) to the rats in the ADSC & DAPT-treated group. Rats are sacrificed at 4, 7, 14 and 28 d post-MCAO. The amount of microvessels was quantified. And the levels of Notch1, Dll4 and Hes1 were detected by Western blot and immunohistochemistry.


RESULTS
The density of microvessels significantly increased in the ADSC group (13.93 ± 0.50, 17.90 ± 0.62, 20.78 ± 0.80, 17.28 ± 1.65) versus the MCAO group (7.03 ± 0.22, 10.83 ± 0.63, 16.35 ± 0.54, 13.80 ± 2.38) (P < 0.05) and the ADSC + DAPT group (5.73 ± 0.30, 7.58 ± 0.52, 7.65 ± 0.45, 6.48 ± 1.47) (P < 0.05). And compared with the MCAO group (1.29 ± 0.07, 2.13 ± 0.21, 1.92 ± 0.03) and the ADSC + DAPT group (1.162 ± 0.099, 1.684 ± 0.180, 1.041 ± 0.040), the expressions of Notch1, Dll4 and Hes1 proteins were significantly up-regulated at 14d in the ADSC group (2.52 ± 0.22, 4.52 ± 0.36, 2.62 ± 0.05) (P < 0.05).


CONCLUSIONS
The transplantation of ADSC can improve angiogenesis by up-regulating the post-MCAO expression of Notch1-Dll4 signaling pathway in rats.
Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Fei-Fei
FF
Lin
Nan
N
Liu
Huan
H
Huang
Ai-Zhen
AZ
Chen
De-Shan
DS
Liu
Xiao-Hui
XH
Lin
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism