脂膜微囊趋向于鼠脑创伤区聚集机制的实验研究  

The mechanisms of lipid-coated microbubbles aggregation toward an injured lesion in rat brain

作　　者：李新钢[1] 宫崧峰[1] 李刚[1] 徐淑军[1] 王东海[1] 张元鹏[1] 何仕玥 

机构地区：[1]山东大学齐鲁医院神经外科,250012 [2]美国康州哈特福德神经外科实验室

出　　处：《中华神经外科杂志》2005年第11期686-690,共5页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金资助项目(30271335);山东省自然科学基金资助项目(Y98C06035)

摘　　要：目的研究脂膜微囊向脑损伤位点靶向性聚集的特点,探讨其向鼠脑损伤区靶向性聚集的机制。方法建立脑损伤动物实验模型,制备脂膜微囊悬液。将脑损伤模型建立成功的28只大鼠随机分为以下几组,损伤当日组、伤后24h组、48h组、72h组、7d组、10d组、14d组、21d组、28d组;分别于损伤后不同时间,由尾静脉注射脂膜微囊悬液,鼠脑标本用油红O染色,研究脂膜微囊在脑损伤后的不同时间在损伤灶周围聚集的特点,并采用双重免疫组化染色,研究增生细胞核抗原(PCNA)及胶原纤维酸性蛋白(GFAP)阳性细胞在损伤灶周围分布的特点,讨论其与脂膜微囊靶向性聚集的关系。结果早期即可在损伤灶周围及损伤灶中发现脂膜微囊,且脂膜微囊密度逐渐增加,48h后可在损伤区的周围发现有微囊以丛集方式聚集;在病损10d左右,微囊的密度最大并聚集成环状。损伤后的第2-3周微囊密度下降至一稳定的水平;GFAP,PCNA双重染色发现了它们各自的密度变化曲线,均在损伤后48h达高峰;GFAP阳性细胞的数量及分布范围远较PCNA范围大,且二者均阳性的细胞数量很少。结论脂膜微囊可靶向性聚集于脑损伤位点周围,不同的时间点微囊的密度不同,损伤后第10天其密度达高峰,脂膜微囊靶向性聚集的机制复杂,与血脑屏障破坏引起的血源性细胞渗出有关,也与反应性星形细胞有关。Objective To investigate the affinity of lipid-coated microbubbles （LCMs） for an injured site in rat brain, and discuss the mechanism of LCM targeting brain lesions. Methods Establish brain injured animal models, and prepare the suspensions of lipid-coated microbubbles. 28 rats were divided into9 groups： the group of 0 hour, 24 hours, 48 hours,72 hours, 7 days, 10 days, 14 days, 21 days, 28 days after injury. The suspension of LCM were given through tail vein injection at different time. Rat brain slices were stained by oil red O to investigate the targeted aggregation characters of LCMs toward brain injured sites. Immunohistochemical double staining was used to investigate the distributional characters of GFAP positive cells and PCNA positive cells around the injured area. And the relationship between LCM targeted aggregation and PCNA and/or GFAP positive cells was discussed. Results LCM began to aggregate toward brain injured site at early stage after injury, and the density of LCM increased gradually. LCM aggregated around the injured site as a circle. At the tenth days after injury, the density of LCM reached its peak, and then declined. The changing curves of GFAP and PCNA positive cells were also found through immunohistochemical double staining. Their peak amount appeared at the point of 48 hours after injury, and then declined. Comparing their distribution area, GFAP positive cells are much larger than PCNA positive cells, but few of them are both positives. Conclusions Lipid-coated microbubbles （LCMs） may targetedly aggregate toward the brain injured site, and at different time their density are different. The density come to its peak at 10 days after injury. The mechanism of targeted aggregation is complicated, maybe related to the damage of blood brain barrier which cause blood cells leakage, also related to the reactive astrocyte.

关 键 词：脂膜微囊 脑损伤 鼠 靶向性聚集机制 

分 类 号：R651.1[医药卫生—外科学]