阿加曲班对实验性大鼠脑出血周围组织神经元损伤的保护作用

目的研究阿加曲班对大鼠实验性大脑内出血的脑保护作用及其可能机制。方法选择SD大鼠60只,按随机数字法分为假手术组(1 2只)、脑出血组(12只)和阿加曲班治疗组(治疗组,36只)。治疗组又按注射阿加曲班1.0、1.5、2.0 mg/kg剂量分为治疗1组(12只)、治疗2组(12只)和治疗3组(12只)。观察应用阿加曲班前后脑出血大鼠神经功能缺损变化情况;应用免疫组织化学和Western blot法,观察阿加曲班干预前后大鼠大脑血肿周围组织中神经元烯醇化酶(NSE)、胶质纤维酸性蛋白(GFAP)阳性神经元数目的变化,以及NSE、诱导型一氧化氮合酶和GFAP表达水平的变化。结果与假手术组和治疗组比较,脑出血组大鼠血肿周围组织中NSE阳性神经元数目明显减少,GFAP阳性神经元数目明显增多,差异有统计学意义(P0.05,P0.01)。与脑出血组比较,治疗组大鼠血肿周围组织中NSE表达水平明显升高,而诱导型一氧化氮合酶及GFAP表达水平明显降低,差异有统计学意义(P0.05,P0.01)。结论阿加曲班可以有效拮抗大鼠脑出血血肿周围组织中NSE的丢失,其机制可能与阿加曲班降低神经元活性氧含量以及抑制炎性反应等作用有关。

The protective effect of argatroban against perihematomal neuron injury in rats with experimental intracerebrai hemorrhage

Objective To investigate the neuroprotective effects of argatroban against perihematomal neuronal injury in rats with experimental intracerebral hemorrhage.Methods Sixty SD rats were randomly divided into three groups:sham-operated group,intracerebral hemorrhage group (ICH group) and argatroban treatment group(three argatroban dosage subgroups:1.0,1.5,2.0 mg/kg).The number of neuron-specific enolase(NSE) positive neurons and glial fibrillary acidic protein(GFAP) positive neurons in perihematomal region was measured by immunohistochemistry. The expression of NSE,inducible nitric oxide synthase (iNOS) and GFAP in perihematomal region was detected by Western blot.Results Compared with argatroban treatment and sham-operated groups.the number of NSE positive neurons was significantly decreased and GFAP positive neurons was significantly increased in the perihematomal region of ICH group (P < 0.05,P < 0.01).After different doses of argatroban treatment(1.0,1.5,2.0 mg/kg) ,NSE expression level obviously increased and iNOS and GFAP expression levels markedly decreased in perihematomal region,the differences were significant compared with ICH group (P < 0.05,P < 0.01).Conclusion Argatroban can effectively block the loss of NSE in perihematomal region of ICH model. The mechanism may be related to its antioxidation and anti-inflammatory activities.