Effects of umbilical cord blood mononuclear cells transplantation via lateral ventricle on the neural apoptosis and the expression of Bax and Bcl-2 proteins in neonatal rats with hypoxic-ischemic brain damage
YAN Shao-Zhen1, WANG Xiao-Li1, WANG Hai-Yu1, DONG Peng1, ZHAO Yan-Song2
Department of Medical Imaging, Weifang Medical University, Weifang, Shandong 261053, China
Abstract Objective To explore the effects of umbilical cord blood mononuclear cells (UCBMC) transplantation on the neuronal apoptosis and the expression of Bcl-2 and Bax proteins in neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into normal control (N)+normal saline (NS), HIBD+NS, N+UCBMC, and HIBD+UCBMC groups. HIBD model was prepared using the classical Rice-Vannucci method. Twenty-four hours after HIBD, UCBMC were transplanted in the N+UCBMC and HIBD+UCBMC groups. Seven days after transplantation, NeuN/Cleaved-Caspase-3 double immunofluorescence staining and TUNEL methods were used to observe neural apoptosis in the cortex. The expression levels of Bax and Bcl-2 proteins were examined by Western blot analysis. Results There were more NeuN+ cleaved Caspase-3+DAPI+ and TUNEL+DAPI+ cells in the HIBD+NS group compared with the N+NS and N+UCBMC groups (P < 0.01). There were less NeuN+ cleaved Caspase-3+DAPI+ and TUNEL+DAPI+ cells in the HIBD+UCBMC group compared with the HIBD+NS group (P < 0.01). The concentration of Bax protein was higher and that of Bcl-2 proteins was lower in the HIBD+NS group compared with the N+NS and N+UCBMC groups (P < 0.01). The concentration of Bax protein in HIBD+UCBMC group was lower than that in the HIBD+NS group (P < 0.01). The concentration of Bcl-2 protein was higher compared with the HIBD+NS, N+NS and N+UCBMC groups (P < 0.05). Conclusions UCBMC transplantation via lateral ventricle can upregulate the expression of Bcl-2 protein and down-regulate the expression of Bax protein, thus alleviating brain neural apoptosis in neonatal rats with HIBD.
YAN Shao-Zhen,WANG Xiao-Li,WANG Hai-Yu et al. Effects of umbilical cord blood mononuclear cells transplantation via lateral ventricle on the neural apoptosis and the expression of Bax and Bcl-2 proteins in neonatal rats with hypoxic-ischemic brain damage[J]. CJCP, 2016, 18(9): 862-866.
YAN Shao-Zhen,WANG Xiao-Li,WANG Hai-Yu et al. Effects of umbilical cord blood mononuclear cells transplantation via lateral ventricle on the neural apoptosis and the expression of Bax and Bcl-2 proteins in neonatal rats with hypoxic-ischemic brain damage[J]. CJCP, 2016, 18(9): 862-866.
Gill MB, Bockhorst K, Narayana P, et al. Bax shuttling after neonatal hypoxia-ischemia:hyperoxia effects[J]. J Neurosci Res, 2008, 86(16):3584-3604.
[2]
Northington FJ, Chavez-Valdez R, Martin LJ. Neuronal cell death in neonatal hypoxia-ischemia[J]. Ann Neurol, 2011, 69(5):743-758.
[3]
Rosenkranz K, Kumbruch S, Tenbusch M, et al. Transplantation of human umbilical cord blood cells mediated beneficial effects on apoptosis, angiogenesis and neuronal survival after hypoxicischemic brain injury in rats[J]. Cell Tissue Res, 2012, 348(3):429-438.
[4]
Wang XL, Zhao YS, Hu MY, et al. Umbilical cord blood cells regulate endogenous neural stem cell proliferation via hedgehog signaling in hypoxic ischemic neonatal rats[J]. Brain Res, 2013, 1518:26-35.
Rice JE 3rd, Vannucci RC, Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat[J]. Ann Neurol, 1981, 9(2):131-141.
[7]
El-Badri NS, Hakki A, Saporta S, et al. Cord blood mesenchymal stem cells:Potential use in neurological disorders[J]. Stem Cells Dev, 2006,15(4):497-506.
[8]
Buzańska L, Jurga M, Stachowiak EK, et al. Neural stem-like cell line derived from a nonhematopoietic population of human umbilical cord blood[J]. Stem Cells Dev, 2006, 15(3):391-406.
[9]
Zhang H, Li Q, Li Z,et al. The protection of Bcl-2 overexpression on rat cortical neuronal injury caused by analogous ischemia/reperfusion in vitro[J]. Neurosci Res, 2008, 62(2):140-146.
[10]
Liu W, Yue W, Wu R. Overexpression of Bcl-2 promotes survival and differentiation of neuroepithelial stem cells after transplantation into rat aganglionic colon[J]. Stem Cell Res Ther, 2013, 4(1):7.
[11]
Wang YC, Feng GY, Xia QJ, et al. Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats[J]. Apoptosis, 2016, 21(4):404-420.
[12]
Yin F, Guo L, Meng CY, et al. Transplantation of mesenchymal stem cells exerts anti-apoptotic effects in adult rats after spinal cord ischemia-reperfusion injury[J]. Brain Res, 2014, 1561:1-10.
[13]
Vendrame M, Cassady J, Newcomb J, et al. Infusion of human umbilical cord blood cells in a rat model of stroke dosedependently rescues behavioral deficits and reduces infarct volume[J]. Stroke, 2004, 35(10):2390-2395.
