大鼠脑出血后血肿周围脑水肿与 Mip1 表达的关系

摘要： 目的 通过分析大鼠脑出血（ICH）后血肿周围脑组织中 Mip1 的表达， 探索 Mip1 对脑水肿的保护作用。方法 90 只雄性 SD 大鼠随机分为假手术组（n=15）和 ICH 组（n=75）， ICH 组再根据造模后脑出血时间均分为 ICH6 h、 12 h、 1 d、 3 d 和 7 d 组。应用自体股动脉血液建立大鼠尾状核脑出血模型。于上述时点断头处死大鼠， 取血肿周围脑组织。采用 HE 染色观察血肿周围脑组织病理形态学变化， 干/湿质量法测定脑含水量 （BWC）， 免疫组化法检测 Mip1 蛋白的表达。结果 脑出血后血肿周围区域神经元胞体明显变小， 胞浆淡染， 胞质内尼氏体明显减少， 细胞周围出现水肿裂隙， 而假手术组脑组织神经细胞形态未见明显变化。脑出血 6 h 后脑含水量逐渐增高， 在 3 d 时达高峰 （均 P＜0.05）， 7 d 时大致恢复正常 （P＞0.05）。大鼠脑出血后脑组织血肿周围有大量胞质或胞核呈棕色的 Mip1阳性细胞分布， 脑出血 6 h 后 Mip1 蛋白表达水平较假手术组明显升高（均 P＜0.05）， 至 7 d 时大致恢复正常（P＞0.05）。结论 脑出血后血肿周围脑组织中 Mip1 高表达， 并与脑水肿进展趋势基本一致， 提示活化的 Mip1 可能参与出血性脑水肿的病理过程。

The brain edema and Mip1 expression of perihematoma after intracerebralhemorrhage in rat model

△Corresponding Author E-mail： katherine69@yeah.netAbstract:Objective To explore the protective effect of Mip1 on cerebral edema by observing the Mip1 expression ofperihematoma in intracerebral hemorrhage (ICH) rat model. Methods Ninety male SD rats were randomly divided intosham-operated group (n = 15) and ICH group (n = 75). ICH group was equally subdivided into 6 h, 12 h, 1 d, 3 d, and 7 dgroups according to cerebral hemorrhage time, 15 in each group. Hematoma was formed by infusing autologous femoral arteryblood into the right caudate nucleus. Rats were killed at the above time points, brain tissues around hematoma were taked.The pathological morphological changes in brain tissue around hematoma were observed using HE staining. The watercontent of brain (BWC) was measured with dry /wet weight method, and immunohistochemistry was used to analyze theaverage optical density value of Mip1 protein in perihematoma. Results Neuronal cell body of perihematoma wassignificantly decreased after ICH, the cytoplasm light staining, Nissl body reduced obviously in cytoplasm, and edema fissureappeared around cells, however, no obvious changes of nerve cells were detected in sham- operated group. Brain edemagradually increased at 6 h, and reached peak at 3 d (all P＜0.05), then up to normal at 7 d after intracerebral hemorrhage(P＞0.05). A large amount of brown Mip1 positive cells were found to distribute in cytoplasm and nucleus of perihematomaafter intracerebral hemorrhage. The Mip1 protein expression level was higher in 6 h after intracerebral hemorrhage than thatin sham-operated group (all P＜0.05), and returned to normal level at 7 d (P＞0.05). Conclusion The high expression ofMip1 after ICH is in line with the trend of the brain edema development, and shows that the activation of Mip1 mayparticipate in the pathological process of hemorrhagic cerebral edema.