Bcl-2腺病毒/E1B 19kD相互作用蛋白3对弥漫性轴索损伤后少突胶质细胞凋亡的调控作用

Role of Bcl-2 adenovirus/E1B 19kD interacting protein 3 in oligodendrocyte apoptosis after diffuse axonal injury

目的探讨Bcl-2腺病毒/E1B 19kD相互作用蛋白3(BNIP3)对大鼠弥漫性轴索损伤(DAI)后少突胶质细胞凋亡的调控作用。方法 77只SD雄性成年大鼠随机分为假手术组(11只)、DAI组(33只)及干预组(33只)。参照Marmarou方法制做DAI模型,干预组大鼠在打击后立即给予脑室注射BNIP3抑制剂necrostatin-1 (Nec-1,30 g/L,2μl),检测Nec-1干预前后DAI大鼠BNIP3蛋白表达,少突胶质细胞凋亡以及髓鞘的组织病理学变化。结果与假手术组相比,大鼠DAI损伤后脑干组织BNIP3表达上调,且与细胞凋亡成正相关;Nec-1干预有效降低DAI大鼠少突胶质细胞BNIP3蛋白表达,显著减少DAI大鼠少突胶质细胞凋亡的数目,提高DAI大鼠脑干髓鞘劳克坚牢蓝(LFB)染色平均吸光度和髓鞘碱性蛋白(MBP)表达,改善DAI大鼠脑干髓鞘的超微结构。结论 BNIP3参与DAI诱导的少突胶质细胞凋亡,抑制BNIP3可保护DAI大鼠少突胶质细胞和髓鞘。

Objective To investigate the role of Bcl-2 adenovirus/E1B 19kD interacting protein 3( BNIP3) in oligodendrocyte apoptosis after diffuse axonal injury( DAI) in rats. Methods Seventy-seven male adult Sprague-Dawley rats were randomly divided into sham group( n = 11),DAI group( n = 33),and intervention group( n = 33). DAI model was made referring to modified Marmarou method and the rats in intervention group received intracerebroventricular injection of BNIP3 inhibitor,necrostatin-1( Nec-1,30 g/L,2 μl) immediately after injury. Tested the BNIP3 protein expression,oligodendrocyte apoptosis and myelin histopathology before and after the intervention of Nec-1. Results Compared with the sham group,DAI rats upregulated BNIP3 levels and had positive correlation with cell apoptosis in brainstem. Nec-1 significantly inhibited BNIP3 expression,then decreased the number of apoptotic oligodendrocytes,increased the average absorbance of luxol fast blue( LFB) staining and myelin basic protein( MBP) levels, and alleviated the myelin ultrastructure of DAI rats. Conclusion BNIP3 participate in the DAI-induced apoptosis of oligodendrocytes,and inhibition of BNIP3 can protect oligodendrocytes and myelin sheath from DAI injury.