关键词: 脑出血, 大鼠神经生长因子, BMSCs-源外泌体, Keap1 / NQO1 / Nrf2 信号通路, 神经损伤

Abstract: Objective To explore the therapeutic effect and mechanisms of rat nerve growthfactor (RtNGF) combined with bone marrow mesenchymal stem cell-derived exosomes ( BMSCs exosomes) on neural injury of intracerebral haemorrhage (ICH) rats. Methods The BMSCs exosomes were prepared for the following experiments. Sixty rats were randomly divided into 5 groups: Sham group, ICH group, ICH + RtNGF group, ICH + BMSCs exosomes group, and ICH + RtNGF + BMSCs exosomes group, with 12 rats in each group. A ICH rat model was established and RtNGF or BMSCs exosomes were treated alone or in combination. Paraffin embedded tissue sections of rat brain tissues in each group were prepared and HE staining was performed. qPCR and Immunohistochemistry were used to determine the mRNA and protein expression levels of genes in the Keap1 / NQO1 /Nrf2 signaling pathway. Results Significant existence of tissue lacunes and blood clots were observed in the ICH group rather than in the Sham group. RtNGF or / and BMSCs treatments improved that situation, and the combination of RtNGF and BMSCs exosomes treatment had the best effect on alleviating neural injury. The mRNA expression levels of Keap1, NQO1 and Nrf2 in the brain tissues, and the IHC relative staining scores of the three proteins in the ICH group were increasedwhen compared with those in the Sham group ( allP < 0. 05). The levels of the above indicators inthe ICH + RtNGF group, ICH + BMSCs exosomes group, and ICH + RtNGF + BMSCs exosomesgroup were decreased when compared with those in the ICH group (P< 0. 05), with the values the lowest in the ICH + RtNGF + BMSCs exosomes group ( P < 0. 05). Conclusion RtNGF combinedwith BMSCs exosomes has significant effect on reducing oxidative stress and alleviating neural injury through Keap1 / NQO1 / Nrf2 signaling pathway in ICH rats.

Key words: