缺氧缺血性脑损伤新生大鼠微管相关蛋白Tau表达与脑细胞凋亡的关系

Relationship of Expression of Microtubule-Associated Protein Tau and Neurocte Apoptosis in Neonatal Rats with Hypoxic-Ischemic Brain Damage

目的观察微管相关蛋白Tau在缺氧缺血性脑损伤(HIBD)新生大鼠脑组织中的表达变化,探讨HIBD早期Tau蛋白与细胞凋亡的关系。方法新生7日龄Wistar大鼠80只,随机分为2组:假手术组和HIBD组,每组各40只。HIBD组采用Rice方法建立新生大鼠HIBD模型。分别于手术后3、6、12、24、48 h取其脑组织切片,采用免疫组织化学方法检测其脑室周围白质区Tau的表达,末端脱氧核苷酸转移酶缺口标志(TUNEL)法检测其神经细胞凋亡。假手术组不行缺氧缺血处理,采用同样方法检测其Tau蛋白及神经细胞凋亡。结果假手术组脑室周围白质有少量Tau表达,且有少量凋亡细胞,各时间点无明显变化(Pa>0.05);HIBD组Tau的表达在6 h后开始增加,24 h达高峰,并持续至48 h,与假手术组比较差异均有统计学意义(Pa<0.05);细胞凋亡在6 h即开始增加,在12、24、48 h逐渐增加,与假手术组比较差异均有统计学意义(Pa<0.05);直线相关回归分析显示不同时间点HIBD组Tau蛋白表达与细胞凋亡呈显著正相关(Pa<0.05)。结论HIBD可造成新生大鼠脑室周围白质中神经纤维变性及Tau蛋白表达增加;Tau蛋白表达异常对促进神经细胞凋亡起重要作用。

Objective To observe the expression of microtubule - associated protein Tau in brain tissue of neonatal rats with hypoxic - ischemic brain damage（HIBD） and its relationship with neurocyte apoptosis. Methods Eighty 7 - day newborn Wistar rats were randomly divided into 2 groups：sham operation group（ n = 40） and HIBD group（ n = 40）. HIBD models were established according to Rice＇s method. At 3 h,6 h, 12 h,24 h and 48 h after hypoxia - ischemia,the brain tissue of rats in HIBD group was obtained to prepare section. The expression of Tau in periventricular white matter was detected by immunohistochemical techniques. The apoptosis of the periventricular white matter was detected by terminal deoxynucleotidytranferase - mediated2 - deoxyuridine5＇ - riphosphate - biotin nick end labeling （TUNEL） staining. The sham operation group was dealt with the same method without hypoxia - ischemia. Results The expression of Tau in periventricular white matter cells significantly increased at 6h after HIBD, peaked at 24 h,and lasted till 48 h,compared with that of sham operation group（Pa〈 0.05）. Fewer Tau expression and TUNEL - positive cells were found in sham operation group, compared with a marked increase in HIBD group;which began at 6h,and continued to go up at 12,24 and 48h,with significant statistical differences in HIBD group, and the elevated levels of Tau and neuronal apoptosis had significant correlations at different time （ Pa 〈 0.05 ）. Conclusions HIBD can cause nerve fiber degeneration in the brain oeriventricular white matter of neonatal rats. The level of Tau increases and the continuous activation of Tau palys an important role in the development of neuronal apoptosis in neonatal rats after HIBD.