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抑制微小RNA-103a可抑制海马组织中星形胶质细胞的活化,并通过调节脑源性神经营养因子改善癫痫大鼠神经元的病理损伤。

Inhibition of microRNA-103a inhibits the activation of astrocytes in hippocampus tissues and improves the pathological injury of neurons of epilepsy rats by regulating BDNF.

作者信息

Zheng Ping, Bin He, Chen Wei

机构信息

1Department of Neurosurgery, Shanghai Pudong New Area People's Hospital, No 490, South Chuanhuan Road, Shanghai, 201299 People's Republic of China.

2Department of Neurosurgery, First affiliated Hospital of Nanchang University, Nanchang, China.

出版信息

Cancer Cell Int. 2019 Apr 24;19(1):109. doi: 10.1186/s12935-019-0821-2. eCollection 2019.

Abstract

BACKGROUND

The aim of this study is to explore the effect of microRNA-103a (miR-103a) on astrocytes activation and hippocampal neuron injury in epilepsy rats by targeting brain-derived neurotrophic factor (BDNF).

METHODS

The epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were intralateroventricularly microinjected with miR-103a inhibitors, inhibitors negative control (NC), siRNA-NC and BDNF-siRNA, respectively. The RT-qPCR and western blot analysis were used to detect the expression of miR-103a, BDNF and glial fibrillary acidic protein (GFAP) in hippocampus tissues of rats. TUNEL staining was used to detect the apoptosis of hippocampal neurons. The RT-PCR and ELISA was used to detect the levels of TNF-α and IL-6 in hippocampal tissues and in serum, respectively.

RESULTS

Increased expression of miR-103a, GFAP, and number of apoptotic neurons, decreased expression of BDNF and number of surviving neurons were found in hippocampus tissues of epilepsy rats. After miR-103a inhibitors interfered with epilepsy rats, there showed decreased expression of miR-103a and GFAP, increased expression of BDNF and decreased number of apoptotic neuron as well as increased number of surviving neurons. Compared with miR-103a inhibitors alone, epilepsy rats treated with BDNF-siRNA combined with miR-103a inhibitors significantly increased expression of GFAP in hippocampal tissues of epilepsy rats, increased number of apoptotic neurons and significantly decreased the number of surviving neurons.

CONCLUSION

Our study provides evidence that the inhibition of miR-103a can inhibit the activation of astrocytes in hippocampus tissues and improve the pathological injury of neurons of epilepsy rats by regulating BDNF gene.

摘要

背景

本研究旨在通过靶向脑源性神经营养因子(BDNF)探讨微小RNA-103a(miR-103a)对癫痫大鼠星形胶质细胞活化和海马神经元损伤的影响。

方法

腹腔注射氯化锂-匹罗卡品诱导癫痫大鼠模型。将成功建模的大鼠分别侧脑室内微量注射miR-103a抑制剂、抑制剂阴性对照(NC)、siRNA-NC和BDNF-siRNA。采用RT-qPCR和蛋白质印迹分析检测大鼠海马组织中miR-103a、BDNF和胶质纤维酸性蛋白(GFAP)的表达。TUNEL染色检测海马神经元凋亡情况。分别采用RT-PCR和ELISA检测海马组织及血清中TNF-α和IL-6水平。

结果

癫痫大鼠海马组织中miR-103a、GFAP表达增加,凋亡神经元数量增多,BDNF表达降低,存活神经元数量减少。miR-103a抑制剂干预癫痫大鼠后,miR-103a和GFAP表达降低,BDNF表达增加,凋亡神经元数量减少,存活神经元数量增加。与单独使用miR-103a抑制剂相比,BDNF-siRNA联合miR-103a抑制剂处理的癫痫大鼠海马组织中GFAP表达显著增加,凋亡神经元数量增加,存活神经元数量显著减少。

结论

我们的研究提供了证据,即抑制miR-103a可通过调节BDNF基因抑制海马组织中星形胶质细胞的活化,改善癫痫大鼠神经元的病理损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e72/6482545/d818168035f9/12935_2019_821_Fig1_HTML.jpg

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