HET0016联合亚低温对缺氧缺血性脑病新生猪仔脑神经元m-calpain蛋白表达的影响  

Effect of HET0016 combined with mild hypothermia on expression of m-calpain protein in cerebral neurons of neonatal piglets with hypoxic-ischemic encephalopathy

作　　者：朱俊超[1] 白文娅 杨延超[1] 滕秀飞 张焕焕[1] 李阳[1] 万玉骁 张勇[2] Raymond C. Koehler 

机构地区：[1]中国医科大学附属盛京医院麻醉科,沈阳市110016 [2]中国医科大学病理学院,沈阳市110001 [3]约翰霍普金斯医学院麻醉与重症医学科

出　　处：《中华麻醉学杂志》2016年第4期505-507,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81401231）

摘　　要：目的评价HET0016联合亚低温对缺氧缺血性脑病新生猪仔脑神经元m—calpain蛋白表达的影响。方法健康新生猪仔36头，雌雄不拘，采用随机数字表法分为4组：假手术组（s组，n=6）、缺氧缺血常温组（HI＋NT组，n=6）、缺氧缺血亚低温组（HI＋MH组，n=12）、缺氧缺血＋HET0016（HET0016）联合亚低温组（HI＋HET＋MH组，n=12）。采取麻醉下吸入低氧浓度一窒息法，建立缺氧缺血性脑病新生猪仔模型。HI＋MH组及HI＋HET＋MH组在建立缺氧缺血性脑病模型后3h，用冰袋将体温降至34℃。HI＋HET＋MH组在循环恢复后3min时静脉输注HET00161mg／kg。独立喂养10d后麻醉下取脑组织标本，采用免疫组化法确定壳核、感觉皮层、海马CA3及丘脑腹后外侧核m—calpain蛋白的表达水平。结果与S组比较，其他各组不同脑区m—calpain蛋白表达上调（P〈0．05）；与HI＋NT组比较，HI＋MH组和HI＋HET＋MH组各脑区m—calpain蛋白表达下调（P〈0．05）；与HI＋MH组比较，HI＋HET＋MH组各脑区m—calpain蛋白表达下调（P〈O．05）。结论HET0016联合亚低温抑制缺氧缺血性脑病新生猪仔神经元凋亡的机制可能与下调m—calpain蛋白表达有关。Objective To evaluate the effect of HET0016 combined with mild hypothermia on the expression of m-calpain protein in cerebral neurons of neonatal piglets with hypoxic-ischemic encephalopathy （HIE）. Methods Thirty-six healthy neonatal piglets （ 1-2 days after birth） , were randomly divided into 4 groups using a random number table： sham operation group （ S group, n = 6） , hypoxia-ischemia and normothermia group （ HI ＋ NT group, n = 6） , hypoxia-ischemia and mild hypothermia group （ HI ＋ MH group, n= 12）, and hypoxia-ischemia and HET0016 combined with mild hypothermia group （HI＋HET＋ M H group, n = 12）. The model of HIE was established by using inhalation of the low concentration of oxygen and asphyxia under anesthesia. In HI＋MH and HI＋I-IET＋MH groups, the body temperature was cooled down to 34℃ by using the ice packs at 3 h after establishment of the HIE model. In group HI＋HET＋MH, HET0016 1 mg/kg was infused intravenously at 3 min after cardiopulmonary resuscitation. At 10 days after independent feeding, the animals were sacrificed, brains were removed, and brain tissue specimens were obtained for determination of the expression of m-calpain protein in the pntamen, sensory cortex, hippocampal CA3 region, and ventroposterolateral nucleus of the thalamus using the immunohistochemical staining. Results Compared with group S, the expression of m-calpain protein in different brain regions was significantly up-regulated in the other groups （P〈0.05）. Compared with group HI＋NT, the expression of m-calpain protein in different brain regions was significantly down-regulated in HI＋MH and HI＋HET＋MH groups （P〈0.05）. Compared with group HI＋MH, the expression of m-calpain protein in different brain regions was significantly down-regulated in group HI＋HET＋MH （P〈0.05）. Conclusion The mechanism by which HETO016 combined with mild hypothermia inhibits neuronal apoptosis may be related to down-regulation of the expression of m-calpain protein in cerebral neu

关 键 词：低温 人工 缺氧缺血 脑 婴儿 新生 神经元 卡配因 HET0016 

分 类 号：R614[医药卫生—麻醉学]