糖尿病酮症酸中毒兔血-脑脊液屏障的变化

目的　探讨糖尿病酮症酸中毒的血脑脊液屏障损伤机制。方法　新西兰家兔随机分模型组(n=6 )和生理盐水对照组 (n=6 )。模型组从耳缘静脉注射四氧嘧啶和链脲佐菌素各 15 0 mg/ kg,对照组给予等量生理盐水 ,72 h后检测血糖、尿酮体。两组静脉内均注射伊文氏蓝 ,6 h后检测动脉血气 ;处死动物 ,取脑组织用紫外分光光度计测定伊文氏蓝吸光度 (A) ,并观察光镜、超微结构、碱性磷酸酶细胞化学及诱导型一氧化氮合酶 (i NOS)免疫组织化学结果。结果　 72 h后模型组 :血糖全部大于 17mm ol/ L,尿中出现酮体 ;伊文氏蓝 A值略增高 ,和对照组相比无显著性差异。组织学和超微结构观察模型组脑血管周围水肿 ,内皮细胞损伤 ,神经元变性、坏死。碱性磷酸酶细胞组化显示血管内皮上酶活性明显弱于对照组。免疫组化可见脑实质内血管壁上 i NOS染色阳性。结论　在四氧嘧啶和链脲佐菌素诱发的糖尿病酮症酸中毒动物模型中出现脑水肿 ,其产生与血脑脊液屏障的破坏及一氧化氮 (NO)参与有关。

Changes of blood-cerebrospinal fluid barrier in rabbits with diabetic ketoacidosis

Objective To explore the mechanism of the changes of blood-cerebrospinal fluid barrier in rabbits with diabetic ketoacidosis(DKA). Methods The New Zealand rabbits were injected with 150 mg/kg streptozotion and alloxan monohydrate each (model group, n=6) intravenously, or equal volume of normal saline (control group, n=6). After 72 hours, blood sugar and uric ketone were detected. All of animals were injected with Evans blue(EB). After 6 hours, arterial blood gases were measured and animals were killed. Absorbency of EB of brain tissue was detected. All brains of animals were examined with light and electron microscopy. Marker of blood-cerebrospinal fluid barrier, cytochemical stains of alkaline phosphatase (ALPase) was operated by ultrastructure. The inducible nitric oxide synthase (iNOS) in brain tissue was detected by immunohistochemical method. Results The models of DKA were established after 72 hours of injecting streptozotion and alloxan monohydrate. Absorbency of EB of model group rabbits was slightly increased, but had no significant difference compared with controls(P>0.05). The brain edema, damages of vessel endothelium and necrosis of neuron were observed through histological and ultrastructure examination in model group. ALPase activity of model group was evidently decreased in brain blood vessel endothelium in comparison with controls. Compared to controls, the iNOS activity of model group was increased and it's positive cells were aggregated on blood vessel of brain membrane. Conclusion By streptozotion and alloxan monohydrate inducing DKA models, NO could induce blood-cerebrospinal fluid barrier damages and result in brain edema.