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目的研究环磷酰胺对大鼠脑出血血肿周围组织NF-κB表达和白细胞浸润的影响。方法健康雄性SD大鼠125只,随机分成3组:假手术组(25只)、对照组(50只)、治疗组(50只),采用Fredrik建立的自体股动脉取血并向大鼠尾壳核注射方法复制脑出血模型。各组按术后6,24,48,72h及5d分为5个时间点,经尾壳核行冠状切片,分别按干湿重法测脑含水量,免疫组织化学法测定NF-κB的表达,HE染色测定血肿周围组织白细胞浸润。结果假手术组各时间点NF-κB表达及白细胞浸润无明显变化。治疗组除6h、24h外,各时间点血肿周围脑组织含水量、白细胞浸润及NF-κB表达均低于对照组(P<0.05)。NF-κB表达与白细胞浸润呈现同步性,而且NF-κB的表达高峰时间先于血肿周围组织白细胞浸润。结论环磷酰胺具有减低NF-κB活性,抑制脑出血血肿周围组织的炎症反应起到神经保护作用。
Objective To study the effect of cyclophosphamide on the expression of NF-κB and leukocyte infiltration in the perihematomal brain tissue of intracerebral hemorrhage in rats. Methods 125 healthy male Sprague-Dawley rats were randomly divided into three groups: sham operation group (n = 25), control group (n = 50) and treatment group (n = 50). Blood was drawn from the autologous femoral artery Intramuscular injection of intracerebral hemorrhage model. The rats in each group were divided into 5 time points at 6, 24, 48, 72h and 5d after operation. Coronal sections of the caudate putamen were used to measure the brain water content by dry-wet method. The expression of NF-κB was measured by immunohistochemistry Hematoxylin and eosin (HE) staining was used to determine the infiltration of leukocytes in the perihematoma tissue. Results There was no significant change of NF-κB expression and leukocyte infiltration in sham operation group at each time point. In the treatment group, the water content, the infiltration of leukocytes and the expression of NF-κB in the perihematoma brain tissue were all lower than those in the control group (P <0.05) except 6h and 24h. The expression of NF-κB and leukocyte infiltration showed synchronization, and the peak time of NF-κB expression was earlier than the leukocyte infiltration in the hematoma. Conclusion Cyclophosphamide has a neuroprotective effect of reducing the activity of NF-κB and inhibiting the inflammatory reaction in the tissues around the hematoma of intracerebral hemorrhage.