miRNA-125a靶向调控Bcl-2对癫痫大鼠神经元凋亡的影响  

Effect of miRNA-125a Targeted Regulation of Bcl-2 on Neuronal Apoptosis in Epileptic Rats

作　　者：裴静[1] 陈明[1] 高华[1] 白杨 王萍[1] PEI Jing;CHEN Ming;GAO Hua;BAI Yang;WANG Ping(Department of Neurology,The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第五附属医院神经内科,乌鲁木齐830000

出　　处：《实验动物科学》2021年第1期23-28,共6页Laboratory Animal Science

摘　　要：目的探讨miRNA-125a靶向调控Bcl-2对癫痫大鼠神经元凋亡的影响.方法选择清洁级SD雄性大鼠32只随机分为正常对照组(A组)、癫痫组(B组)、miRNA-125a antagomir control组(C组)和miRNA-125a antagomir组(D组).qRT-PCR检测各组大鼠脑组织miRNA-125a表达水平;HE检测各组大鼠脑海马组织CA-1区病理形态学改变;TUNEL法检测脑海马CA-1区神经元细胞凋亡数;Western blot和qRT-PCR法检测各组大鼠脑组织中Bcl-2的表达水平;荧光素酶活性检测miRNA-125a与Bcl-2的靶向关系.结果与A组相比,B组和C组大鼠脑组织miRNA-125a表达升高,差异具有统计学意义(P<0.05);A组海马细胞排列整齐,细胞形态结构及层次清晰完整,核仁明显,间质无水肿;B组可见坏死灶,细胞排列紊乱,细胞核固缩,核仁消失,细胞间隙增宽出现水肿;TUNEL结果显示,B组、C组和D组脑海马神经元凋亡细胞数明显高于A组,而大鼠脑组织Bcl-2 mRNA及蛋白表达降低.D组miRNA-125a表达与C组相比降低而Bcl-2表达增加(P<0.05),且D组大鼠脑组织水肿现象明显减轻,海马细胞排列紊乱现象有所改善.荧光素酶报告基因实验结果显示,miRNA-125a和Bcl-2能够靶向结合.结论癫痫模型大鼠脑组织miRNA-125a可通过调控Bcl-2表达,进一步导致脑海马神经元损伤及大量神经元细胞凋亡;抑制miRNA-125a的表达水平可改善癫痫大鼠神经元损伤.Objective To investigate the effect of miRNA-125a targeting Bcl-2 on neuronal apoptosis in epileptic rats.Method Thirty two male SD rats were randomly divided into normal control group(group A),epilepsy group(group B),miRNA-125a antigomir control group(group G)and miRNA-125a antigomir group(group D).The expression level of miRNA-125a was detected by qRT-PCR.HE was used to detect the pathomorphological changes of CA-1 region in hippocampus in each group.TUNEL method was used to detect the apoptosis number of neurons in CA-1 region in hippocampal.Western blot and qRT-PCR were used to detect the expression of Bcl-2 in brain tissue of rats in each group.The targeting relationship between miRNA-125a and Bcl-2 was detected by luciferase activity.Result Compared with group A,the expression of miRNA-125a in brain tissue of group B and group C increased significantly(P<0.05).In group A,hippocampal cells were arranged orderly,cell morphology and structure were clear and complete,nucleolus was obvious,interstitial tissue had no edema;in group B,necrosis was seen,cell arrangement was disordered,nuclear pyknosis and nucleolus disappeared,cell gap widened and edema appeared.The result of TUNEL showed that the number of apoptotic cells in hippocampus of group B,C and D was significantly higher than that of group A,while the expression of Bcl-2 mRNA and protein was decreased.The expression of miRNA-125a in group D was lower than that in group C,while the expression of Bcl-2 in group D was higher than that in group C(P<0.05).The result of luciferase reporter gene experiment showed that miRNA-125a and Bcl-2 could target to combine.Conclusion The expression of miRNA-125a in brain tissue of epileptic rats can be further regulated by Bcl-2,which can further lead to brain horse neuron injury and a large number of neuron apoptosis;inhibition of miRNA-125a expression level can improve the neuron injury of epileptic rats.

关 键 词：miRNA-125a BCL-2 癫痫 神经元 凋亡 

分 类 号：R741[医药卫生—神经病学与精神病学]