摘要
目的探讨冰片开放血-脑脊液屏障(BCB)对实验性细菌性脑膜炎治疗的影响。方法采用日本大耳白兔作为实验动物,随机分为对照组、冰片组和脑膜炎组。经枕大池注入肺炎球菌悬液建立脑膜炎模型,以冰片作为开放BCB的制剂。以连续静脉注射丙戊酸钠后不同时间点的脑脊液中丙戊酸钠浓度变化作为判断BCB通透性的指标;硝酸镧示踪法观察脑组织表现作为BCB通透性的形态指标。给予脑膜炎动物头孢吡肟或冰片+头孢吡肟治疗,记录动物存亡情况;取脑脊液(CSF)进行细胞计数及生化检查,取脑组织作常规病理染色,以观察冰片开放BCB对实验性细菌性脑膜炎治疗的影响。结果给药后对照组CSF中丙戊酸钠浓度基本保持稳定,冰片组CSF中丙戊酸钠浓度于给药后0.5h时即高于对照组并逐渐上升,至6h时达高峰,然后开始下降,14h时浓度仍高于对照组。脑组织超微结构显示,对照组无硝酸镧颗粒通过BCB,脑膜炎组硝酸镧颗粒分布于毛细血管基底膜外,冰片组弥漫性分布于神经细胞间隙和轴突周围。给予头孢吡肟治疗后,脑膜炎+冰片组动物存活率(9/12,75%)明显高于脑膜炎组(6/18,66.7%)(P<0.05),但两组间CSF细胞数及蛋白、葡萄糖水平差异无统计学意义。近皮层脑组织HE染色显示,脑膜炎组可见脑组织大量炎症细胞渗出和软化坏死灶,血管“套袖”现象明显,而脑膜炎+冰片组脑组织内炎症细胞渗出较少,无血管“套袖”现象,无明显坏死软化灶。结论冰片确实能明显增加BCB的通透性并具有可逆性特点,抗生素联合冰片能改善实验性细菌性脑膜炎治疗效果,为细菌性脑膜炎的治疗提供了新的思路。
ABSTRACT： Objective To explore the opening effect on the blood-cerebrospinal barrier （BCB） induced by borneol （Bn） and its improvement of antibiotic treatment for experimental bacterial meningitis. Methods Japanese big-ear white rabbits were randomly divided into experimental meningitis, Bn used and control groups. The experimental meningitis was infected by the injection of pneumococci into the cistern magna. Bn was drenched to open the BCB. The concentrations of Valproate sodium （Vs） in CSF as the index of BCB opening were monitored at the different time points after injection of Vs. Using lanthanum nitrate as a tracer, ultrastructursl integrity of the BCB and brain tissue was observed under electron microscope. The animals with experimental meningitis were treated by Cefepime or a combination of Cefepime with Bn. Survival rate and mortality were recorded. CSF analysis, and neuropathological observation of the brains in these two groups were evaluated. Results group, while in Bn The concentration of Vs in CSF was steady from 0. 5 h to 14 h after injection of Vs in control used group was higher at 0. 5 h and thereafter, reached a peak at 6 h, still higher at 14 h. Ultrastructural observation revealed that lanthanum granules were only located within the capillary wall in control group, but they moved out of capillary basement membrane in meningitis group, and spread to the inter-neuronal spaces and around neuronal axons in Bn used group. Combined the administration of Cefepime with Bn, the survival rate of the animals with meningitis（9/12,75%）was obviously higher than that in the group only treated by Cefepime（6/18,66.7% ）（P〈0.05）. However, CSF cell count and biochemical parameters in two groups were not statistically different. Pathological study showed that near the subarachnoid space lots of inflammatory cells infiltrated and the necrotic foci were with vessel ＂cuff＂ in Cefepime treated meningitis group, while in Cefepime and Bn combination group there were few inflammatory cells and without vessel ＂cuff＂ in the necrotic foci. Conclusions The present study confirms that Bn did increase the permeability of BCB with reversibility. The combining treatment with antibiotics and Bn may improve the outcome of experimental bacterial meningitis including the decrease of mortality and amelioration of local inflammation. This would give us a new idea for the treatment of bacterial meningitis.
出处
《中国神经免疫学和神经病学杂志》
CAS
2007年第2期93-96,共4页
Chinese Journal of Neuroimmunology and Neurology
基金
首都医学发展基金资助项目(2002-2027)
关键词
冰片
血-脑脊液屏障
实验性细菌性脑膜炎
borneol
blood cerebrospinal fluid barrier
experimental bacterial meningitis
