Effects Of Adipose-derived Stem Cells Transplantation On Angiogenesis In The Brains Of Rats With Focal Cerebral Ischemia And Its Mechanism Study

Object: To investigate the effects of adipose-derived stem cells (ADSCs) transplantation on the angiogenesis in the brains of rats with focal cerebral ischemia. And to investigate the role of Notch1-Dll4 signaling pathway in the brains of MCAO rats by detectting the expression of Notch1-Dll4 signaling pathway.Methods: Adipose-derived stem cells were harvested and purified following adherence technique. Sixty-five male adult Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group (Sham group), cerebral ischemia group (MCAO group), ADSCs-treated group (ADSCs group), ADSCs and DAPT-treated group (DAPT group). A permenant focal cerebral ischemia model was established using modified Zea-Longa's method. 24 hours after middle cerebral artery occlusion (MCAO), 1 x 106 ADSCs labeled by DAPI were injected into the lateral ventricle of rats in ADSCs-treated group and the same dose of ADSCs contained DAPT (Notch signaling pathway inhibitor) were given to the rats in ADSCs and DAPT-treated group. Rats are sacrificed at 4d, 7d, 14d and 28d after MCAO. The amount of microvessel was counted, and the levels of Notch1, Dll4, and Hes1 were detected by Western-bolt and immunohistochemical method.Results: DAPI staining positive cells were observed around the cerebral infarcted area after ADSCs transplantation. The amount of microvessels significantly increased in ADSCs group compared with the MCAO group and the DAPT group (P<0.05). And compared with the MCAO group and the DAPT group, the Notch1, Dll4, and Hes1 protein expressions in in ADSCs group were significantly upregulated (P<0.05).Conclusions:1. ADSCs transplatation can obviously improve the angiogenesis in the brains of rats with focal cerebral ischemia. 2. ADSCs transplantation can upregulate the expression of Notch1-Dll4 signaling pathway, and this effect can be reversed by Notch signaling pathway inhibitor DAPT.3. ADSCs transplantation can improve the angiogenesis by upregulating the expression of Notch1-Dll4 signaling pathway in rats after MCAO.