摘要： 目的 观察前列地尔对实验性脑出血模型大鼠血肿周围组织神经元形态的影响。方法 采用立体定向技术于右侧基底节注射自体动脉血制备脑出血大鼠模型。前肢伸置和转身运动测验评价大鼠行为学变化，尼氏染色观察不同处理组大鼠血肿周围组织神经元形态变化，间接免疫荧光染色计数血肿周围组织TNF-α和IL-6 表达阳性细胞数目及分布范围。结果 脑出血后大鼠行为障碍主要表现为运动感觉损伤和动作不对称，给予前列地尔治疗后其症状与体征明显改善，且于实验第5、7 和14 天时行为功能恢复程度接近对照组（P < 0.05 或P < 0.01）。组织形态学观察可见，脑出血后血肿周围组织有大量炎性细胞浸润、坏死，呈现“挤压区”，其外侧细胞水肿、轮廓不清；经前列地尔治疗后炎性细胞浸润和神经元肿胀不同程度改善，且随着治疗时间的延长脑出血同侧正中裂旁皮质区神经元数目逐渐增加，至治疗结束时接近正常水平（P = 0.650）。脑出血后血肿周围组织神经元高表达TNF-α和IL-6，阳性细胞主要分布于血肿周围组织，血肿远隔部位和健侧几乎不表达；经前列地尔治疗后，二者表达水平呈逐渐降低趋势，并于治疗第7（P = 0.035，0.023）和14 天（P = 0.024，0.020）时接近正常水平。结论 前列地尔对脑出血模型大鼠神经功能改善的机制，可能与抑制血肿周围组织炎性反应、减少血肿周围组织继发性神经元损害有关。

关键词: 前列地尔, 脑出血, 血肿, 肿瘤坏死因子α, 白细胞介素6, 疾病模型, 动物

Abstract: Objective To investigate the effect of alprostadil on perihematomal tissue of experimental intracerebral hemorrhage (ICH) in rats. Methods The ICH was induced by stereotaxic infusion of autologous arterial blood into the right basal ganglion. Forelimb placing test and corner turn test were used as behavioral tests. The rats were tested at 3, 5, 7 and 14 d after ICH. Nissl staining was performed to observe the neuronal morphological changes in perihematomal tissue. Immunofluorescence staining was used to determine the number and distribution of tumor necrosis factor-α (TNF- α) and interleukin-6 (IL-6) positive cells in perihematomal tissue at 3, 5, 7 and 14 d. Results Alprostadil-treated group showed significant improvement in behavioral tests at 5, 7 and 14 d compared with the control group (P < 0.05 or P < 0.01), but there was no significant difference at 3 d (P = 0.788, 1.000). Nissl staining showed that after cerebral hemorrhage there were obvious inflammatory infiltration, tissue necrosis presented as a "compressed zone" in the perihematomal tissue, and cells around the zone were swollen and had no apparent profile. After alprostadil treatment inflammatory cell infiltration and swollen neurons were reduced in different degrees. Along with the duration of treatment, neuron gradually increased in cortical area beside the medial fissure ipsilateral to the hemorrhagic side, and achieved approximately to normal level at the end of the therapy (P = 0.650). TNF-α and IL-6 positive cells were mainly distributed around the hematoma, while there were few positive cells at the distal and contralateral site. After administration of alprostadil TNF-α positive cells decreased and IL-6 positive cells increased in perihematomal region, and all nearly reached to normal level as the control group at 7 d (P = 0.035, 0.023) and 14 d (P = 0.024, 0.020). Conclusion Alprostadil can improve neurological function of cerebral hemorrhagic rats. The mechanisms may be related to the suppression of acute inflammation and relief of secondary neuron injury around hematomal tissue.

Key words: Alprostadil, Cerebral hemorrhage, Hematoma, Tumor necrosis factor-alpha, Interleukin-6, Disease models, animal