大鼠脑出血周边组织TNF-α、ICAM-1的表达及NAC对其变化的影响

Expression of tumor necrosis factor alpha and intercellular adhesion molecule-1 and the effects of N-acetyl-L-cystein(NAC) on their expression after intracerebral hemorrhage in rat

目的:研究大鼠脑出血周边组织细胞凋亡及TNF-α、ICAM-1(细胞粘附因子-1)的表达机制,探讨NAC(N-乙酰-L-半胱氨酸)抗细胞凋亡作用和对TNF-α、ICAM-1表达的干预机制。方法:W istar大鼠105只,随机分为对照组,脑出血组,脑出血+NAC组,各分为(出血6h,12h,24h,48h,3d,5d,7d)七个时间点。采用立体定位注入自体未肝素化动脉血复制脑出血模型。采用免疫组化染色法检测脑组织ICAM-1的表达;利用原位末端标记法检测出血周边组织神经细胞的凋亡。结果:①脑出血后6h血肿周边组织TNF-α开始表达,48h达高峰,12h ICAM-1开始表达,72h达高峰。各组与对照组之间有显著差异(均P<0.05)。②大鼠脑出血周边组织6h出现凋亡细胞,12h上升显著,3d凋亡细胞达峰值,7d仍有凋亡细胞表达。③NAC干预后周边组织TNF-α、ICAM-1表达阳性细胞数及凋亡细胞数与脑出血组对应时间点比较显著下降(P<0.05)。结论:①细胞因子TNF-α、ICAM-1参与了脑出血周边组织炎性反应损伤。②脑出血周边组织存在着细胞凋亡病理生理过程。③NAC可抑制细胞因子TNF-α、ICAM-1表达,同时具有抗细胞凋亡作用,可改善脑出血预后。

Objective. To Study cell apoptosis and the expression mechanism of tumor necrosis factor alpha （TNF--α） and intercellular adhesion molecule--1 （ICAM--1） and to explore N--acetyl--L--cystein （NAC）anti-- aPoptosis and its influence on TNF--α and ICAM--1 expression after rat intracerebral hemorrhage（ICH）. Methods ： ①One hundred and five Wistar rats were randomly divided into control,ICH and ICH ＋NAC groups. The time was set at 6h, 12h, 2411,48h, 72h, 5d and 7d after ICH in every group. The experimental ICH model was prepared through injection of autologus blood by stereotactic method. ②The expression of TNF--α and ICAM--1 in the cerebral tissue at different time was detected by using immunohistochcnlieal techniques. The apoptosis around hematoma in ICH was determined by using terminal deoxyribo--nueleotide transferase--mediated dUTP--biotin nick end labelling（TUNEL） method. Results .①TNF--α expression started at 6h and reached its peak at 48h,the ICAM--lexpression started at 12h and reached its peak at 72h after rat intracerebral hemorrhage. There were obvious differences between each intraeerebral hemorrhage group and control gruop （all P 〈 0.05 ） ;QE）The apoptosis around hematoma in ICH was detected at 6h and reached the peak at 3d. There still appeared apoptosis expression until 7d; ②The expression of TNF--α and ICAM--1 positive cells and apoptosis significantly decreased, compared with the same time alter NAC interfere around hematoma in ICH, Conclusion：①The TNF--α and ICAM--1 are involved in the imflammatory reaction around hematoma in ICH;②The physiological--pathological process of apoptosis exslts around hematoma ;③NAC can inhibit the expression of TNF-α and ICAM--1, prevent apoptosis and improve prognosis.