摘要
目的研究高碳酸血症对严重低氧缺血大鼠脑损伤的影响及其机制。方法雄性SD大鼠48只,随机分为假手术组(S组)、低氧缺血组(HI组)和高碳酸血症组(HP组),每组16只。S组暴露左侧颈总动脉但不结扎,1h后机械通气,维持PaO_2和PaCO_2在正常水平3h。制作低氧缺血模型,HI组吸入11%~13%O_2并维持PaO_230~49mm Hg;HP组在HI组的基础上吸入11%~13%O_2-8%CO_2-N2混合气维持PaO_230~49mm Hg,PaCO_260~80mm Hg。机械通气3h后处死大鼠,观察脑组织水肿及病理改变,采用TUNEL法检测皮质神经元凋亡,应用FITC-dextran检测血脑屏障通透性的变化,免疫荧光法检测皮质水通道蛋白4(AQP4)及缺血区皮质内皮细胞的标记物(RECA-1)的表达,Western blot法检测AQP4的蛋白含量变化。结果与S组比较,HI组和HP组血脑屏障通透性明显升高,脑含水量明显增加(P<0.05);与HI组比较,HP组脑含水量明显增加(P<0.05),脑组织损伤加重,TUNEL染色阳性细胞数明显增加(P<0.05),脑皮质AQP4蛋白含量明显升高,RECA-1荧光强度明显降低,断离现象明显增多,血脑屏障通透性明显增加(P<0.05)。结论高碳酸血症加重了严重的低氧缺血性脑损伤,其机制可能与脑皮质AQP4蛋白表达的增加和血脑屏障的破坏有关。
Objective To investigate the effect of hypercapnia on hypoxic-ischemic brain injury in rats. Methods Forty-eight adult male SD rats were randomly divided into three groups： sham group （group S）, hypoxic ischemic group （group HI） and hypercapnia group （group HP）, n=16 in each group. Levine＇s model was used to cause hypoxic-ischemic brain injury. In group S, the left com- mon carotid artery was separated without ligation for 1 h, then ventilation with air maintaining the normal levels of PaOz and PaCO2 for 3 h. In group HI, the left common carotid artery was separated and ligated for 1 h, PaOz was maintained at 30-49 mm Hg by ventilating with low concentration （11%-13%） O2 for 3 hours. Based on group HI, PaCOz in group HP was maintain at 60-80 mm Hg by inhalation of mixture gas containing （11%-13%） O2-8%CO2-N2 for 3 hours. FITC-dextran was used to measure the permeability of blood-brain barrier, TUNEL staining were used to observe the changes in the structure of the cerebral cortex. The expressions of aquaporin AQP4 and RECA-1 in cerebral cortex were detected by immunofluorescence and western blot. Results The level of brain water content, permeability of blood brain barrier and AQP4 expression were significantly increased in group HP as compared with group S and group HI （P〈0. 05）. The histopathologic damage, as well as neuronal apoptotic index were aggravated in group HP as compared with group HI （P〈0. 05）. Conclusion Hypercapnia may aggravate the brain damage during severe hypoxic-ischemic brain injury. This may associate with the increased expression AQP4 and the damage of blood-brain barrier.
出处
《临床麻醉学杂志》
CAS
CSCD
北大核心
2017年第5期473-477,共5页
Journal of Clinical Anesthesiology
基金
国家自然科学基金(81171076
81400989)
黑龙江省青年科学基金项目(QC2011C004)
