miRNA-132上调p75ECD和Trk A抑制Aβ对大鼠海马CAI区神经元毒性作用

The inhibitory effect of miRNA-132 on the damage neurons of hippocampus by Aβ via upregulating p75ECD and Trk A in rat

目的探讨miRNA-132调控p75ECD和TrkA抑制Aβ对大鼠海马CAI区神经元损伤的机制。方法将60只健康大鼠分为对照组、Aβ组和miR-132组,每组20只。用免疫组化检测大鼠海马区Trk A的阳性细胞数量;CCK8检测神经细胞活力;TUNEL检测神经细胞凋亡程度;Western blot检测p75ECD、Trk蛋白表达,比较各组差异性。结果 Aβ组海马CAI区Trk A细胞数与对照组相比明显减少,而miR-132组与Aβ组相比明显增多;Aβ组较对照组神经元活性减弱,神经元损伤严重,修复能力缓慢,miR-132组较Aβ组神经元活性增强,神经元损伤程度下降;Aβ组与对照组相比神经元凋亡程度严重,miR-132组较Aβ组神经元凋亡程度减轻;Aβ组与对照组相比神经元中p75ECD、Trk A蛋白表明下降,miR-132组较Aβ组神经元中p75ECD、Trk A蛋白水平上升。结论 miRNA-132过表达可激活p75ECD和Trk A,降低Aβ对神经元的损伤。

Objective To investigate the inhibitory effect of miRNA-132 on the damage neurons of hippocampus by Aβ via upregulating p75 ECD and Trk A in rat. Methods Sixty healthy rats were divided into control group, A beta(Alzheimer’s disease model) group and Aβ transfected group of microRNA-32, 20 rats in each group. Trk A positive cells was detected by immunohistochemistry, the activity of nerve cells was detected by CCK8, the apoptosis nerve cells was detected by TUNEL. The expression of p75 ECD and Trk protein was detected by Western blot. Results The number of TrkA positive cells in hippocampal CAI area was significantly decresed in Aβ group than in control group, but increased in microRNA-32 group than in Aβ group. The activity of neurons was weakened, with serious damaged neurons and lower repair ability in Aβ group than in control, but increased in microRNA-32 group than in Aβ group. The apoptotic rates of neurons was more higher in Aβ group than in control, but lower in microRNA-132 than in Aβ group. The expression levels of p75 ECD and TrkA proteins in neurons were decreased in Aβ group than in control, but increased in microRNA-132 group than in Aβ group. Conclusion Overexpression of MiRNA-132 can activate p75 ECD signal and TrkA receptor, reduce neuronal damage caused by A beta.