低氧复合丙泊酚通过铁死亡对未成熟SD大鼠海马神经元的影响  

Hypoxia aggravates propofol-induced hippocampal neuron injury in immature SD rats through ferroptosis

作　　者：高雯 王维萍 刘玲[1] 杨飞[1] 涂生芬[1] GAO Wen;WANG Weiping;LIU Ling;YANG Fei;TU Shengfen(Department of Anesthesiology,National Clinical Research Center for Child Health and Disorders,Key Laboratory of Child Development and Disorders of Ministry of Education,Chongqing Key Laboratory of Pediatrics,Children’s Hospital of Chongqing Medical University,Chongqing,400014,China)

机构地区：[1]重庆医科大学附属儿童医院麻醉科,国家儿童健康与疾病临床医学研究中心,儿童发育疾病研究教育部重点实验室,儿科学重庆市重点实验室,重庆400014

出　　处：《陆军军医大学学报》2023年第5期380-385,共6页Journal of Army Medical University

基　　金：国家自然科学基金青年科学基金(31200853)。

摘　　要：目的探讨低氧复合丙泊酚通过铁死亡对未成熟SD大鼠海马神经元的影响。方法将168只新生7 d龄SD大鼠(雌雄各半)按随机数表法分为6组[n=28,体质量(15.59±1.13)g]:脂肪乳氧气组(CO)、脂肪乳空气组(CA)、脂肪乳低氧组(CH)、丙泊酚氧气组(PO)、丙泊酚空气组(PA)、丙泊酚低氧组(PH)。丙泊酚组腹腔注射丙泊酚50 mg/kg、脂肪乳组腹腔注射脂肪乳剂5 mL/kg,1次/d,连续7 d。每次注射完毕后分别放入氧浓度为50%、21%、18%的暖箱(38℃),待翻正反射恢复后,即放回常氧环境中由母鼠继续喂养。观察并监测未成熟SD大鼠丙泊酚麻醉后呼吸频率(RR)和血氧饱和度(SpO_(2));透射电镜观察海马神经元内线粒体形态改变;生化法检测海马组织中Fe^(2+)、丙二醛(malondialdehyde,MDA)含量,Western blot检测海马组织中转铁蛋白受体(transferrin receptor,TFRC)的蛋白表达。结果RR和SpO_(2)监测结果显示:与相应的脂肪乳组比较,PO组仅RR降低(P<0.01),而PA组、PH组RR和SpO_(2)均降低(P<0.01)。透射电镜显示:PA组、PH组海马神经元内线粒体普遍肿胀,线粒体嵴溶解、消失。生化法检测结果显示:与相应的脂肪乳组比较,PO组、PA组、PH组Fe^(2+)含量、MDA水平均升高(P<0.01);与PO组比较,PA组、PH组Fe^(2+)含量、MDA水平均升高(P<0.05)。Western blot检测结果显示:与相应的脂肪乳组比较,PO组、PA组、PH组TFRC表达上调(P<0.05);与PO组比较,PA组、PH组的TFRC表达上调(P<0.05)。结论低氧因素增加丙泊酚对未成熟SD大鼠海马神经元的损伤,其机制与海马组织铁死亡相关。ObjectiveTo investigate the effect of hypoxia combined with propofol on immature Sprague-Dawley(SD)rat hippocampal neurons through ferroptosis.MethodsA total of 1687-day-old SD rats(half male and half female,15.59±1.13 g)were randomly divided into 6 groups(n=28):lipid emulsion solvent+50%oxygen(CO),lipid emulsion solvent+air(CA),lipid emulsion solvent+18%oxygen(CH),propofol+50%oxygen(PO),propofol+air(PA),and propofol+18%oxygen(PH)groups.The rats in the propofol group were intraperitoneally injected with 50 mg/kg propofol,and those in the lipid emulsion group were intraperitoneally injected with 5 mL/kg lipid emulsion,once a day for 7 consecutive days.After injection,the mice were put into warm chambers with oxygen concentration of 50%,21%and 18%(38℃)respectively.After the righting reflex recovered,the mice were immediately put back into the normoxic environment for feeding by their mothers.The respiratory rate(RR)and blood oxygen saturation(SpO_(2))of immature SD rats were observed and monitored after propofol anesthesia.The morphological changes of mitochondria in hippocampal neurons were observed by transmission electron microscopy.The contents of Fe^(2+)and malondialdehyde(MDA)in the hippocampus were detected by biochemical assay,and the protein expression of transferrin receptor(TFRC)in the hippocampus was detected by Western blotting.ResultsThe results of RR and SpO_(2)monitoring showed that compared with the corresponding lipid emulsion group,only RR in the PO group was decreased(CO vs PO,P<0.01),while RR and SpO_(2)in the PA and PH groups were decreased(CA vs PA,CH vs PH,P<0.01).Transmission electron microscopy displayed that the mitochondria in the hippocampal neurons of the PA and PH groups were generally swollen,with dissolved and disappeared mitochondrial cristae.The results of the biochemical assay showed that the Fe^(2+)content and MDA level in the PO,PA,and PH groups were increased than those in the corresponding lipid emulsion groups(P<0.01).Compared with the PO group,the content of Fe^(2+)and M

关 键 词：低氧 丙泊酚 铁死亡 未成熟SD大鼠 海马神经元 

分 类 号：R322.81[医药卫生—人体解剖和组织胚胎学] R965.3[医药卫生—基础医学] R971.2