维生素A缺乏影响胶质源性神经营养因子抑制大鼠缺氧缺血脑损伤后细胞增殖的研究

关键词：缺氧缺血脑损伤  维生素A  神经修复  空间记忆  学习  细胞增殖

Keywords:hypoxic-ischemic brain damage  Vitamin A  neurological rehabilitation  spatial memory  learning  cell generation

摘要：

      摘要 目的：研究体内维生素A水平缺乏通过RARα通路抑制大鼠缺氧缺血性脑损伤(HIBD)后神经细胞增殖进而影响脑组织功能恢复。 方法：将74只SD大鼠随机分为假手术组(CON组)、VA正常（VAN组）及VA缺乏组（VAD组），HIBD建模按经典Rice法。Morris水迷宫评估空间记忆力，EDU细胞增殖检测VAN、VAD组HIBD后细胞增殖，更深入剖析皮质组织RA受体、神经标志物的基因水平。 结果：Morris水迷宫实验提示HIBD后恢复晚期VAN组空间记忆力明显强于VAD组（P<0.05）；EDU结果显示,VAN组新生细胞增殖明显强于VAD组（P<0.05）；RARα是各RA受体表达的优势受体。VAN组巢蛋白(Nestin)、神经元特异性烯醇化酶(NSE)、胶质纤维酸性蛋（GFAP）及胶质源性神经营养因子（GDNF）的基因水平明显高于VAD组（P<0.05）。 结论：VA缺乏抑制HIBD后脑组织功能恢复，推测是VA信号下调GDNF从而抑制NSE、Nestin及GFAP表达，进而影响细胞增殖及功能修复。

Abstract:

      Abstract Objective：To study the effect of VA deficiency on the neural function and tissue recovery of hypoxic ischemic injury through RARα pathway to inhibit proliferation of nerve cells in rats. Method：A total of 74 SD rats were randomly divided into VAN（VA normal）、VAD（VA deficiency） and CON(control) groups. HIBD model were created for VAD and van groups according to Rice classical method. The CON group accepted shame operation only. Morris water maze was used to evaluate the neurocognitive function of the rats, EDU was used to evaluate the proliferation function of the experimental group. Furthermore, We analyzed the mRNA levels of RA receptors and neural markers in the cortex. Result：①Function：The Morris water maze test showed that the spatial memory of the VAN group was significantly better than that of the VAD group after HIBD（P<0.05）.②The results of EDU showed that the proliferation of neonatal cells in group VAN was significantly stronger than that in group VAD (P<0.05).③RAR α was the dominant receptor for the expression of RA receptors. Furthermore, the levels of neuronal markers NSE, neural stem marker Nestin, glial cell marker GFAP and neurotrophic factor GDNF in group VAN were significantly higher than those in group VAD (P<0.05). Conclusion：The VA deficiency inhibits the recovery of nerve tissue after HIBD in vivo. The mechanism maybe that the VA signal acts on GDNF that inhibits the action of NSE, Nestin and GFAP, which finally affects the functional rehabilitation of nervous tissue.