1.Effect of hemoglobin on Shp2 expression in brain tissues and adherens junction in blood brain barrier in rats after intracerebral hemorrhage
Zhiguo XING ; Zhen YANG ; Yaping NI ; Jingjun SONG ; Shidong KUANG ; Wei YANG
Chinese Journal of Neuromedicine 2020;19(3):260-265
Objective:To investigate the effect of hemoglobin on Shp2 expression in brain tissues and adherens junction in blood brain barrier in rats after cerebral hemorrhage.Methods:Eighty male SD rats were randomly allocated into sham-operated group and groups of cerebral hemorrhage for 6 h, 24 h, 3 d, and 7 d ( n=16). Rat models in the groups of cerebral hemorrhage were established by intracerebral injection of 20 μL of hemoglobin. Six h, 24 h, 3 d, and 7 d after injection, neurological functions were assessed by Longa scale; brain water content and brain organ coefficient in the harvested cerebral tissues were calculated by wet-dry weighting method; Shp2 mRNA expression was analyzed by real-time fluorescence quantification reverse transcription PCR (qRT-PCR); Shp2 positive neurons was detected by immunohistochemistry; the protein expressions of Shp2, α-catenin, β-catenin and vascular endothelial (VE)-cadherin, and phosphorylated (p-) α-catenin, p-β-catenin and p-VE-cadherin were explored by Western blotting. Results:As compared with those in the sham-operated group, Longa scale scores in groups of intracerebral hemorrhage for 6 h, 24 h, 3 d and 7 d were significantly increased ( P<0.05). As compared with the sham-operated group, groups of intracerebral hemorrhage for 24 h, 3 d and 7 d had significantly increased brain water content and brain organ coefficient, statistically reduced Shp2 mRNA expression, statistically samller amount of Shp2 positive neurons, and statistically reduced Shp2 protein expression, and significantly increased protein expressions of p-α-catenin, p-β-catenin and p-VE-cadherin ( P<0.05). Conclusion:Intracerebral injection of hemoglobin can downregulate Shp2 expression and promote phosphorylation of adherens junction proteins, therefore induce the disruption of adherens junction, which might be a critical mechanism of blood-brain barrier disruption and brain edema.