目的 分析脑苷肌肽对缺氧缺血性脑病（HIE）新生大鼠环磷酸鸟苷-腺苷合成酶（cGAS）/膜蛋白干扰素基因刺激因子（STING）通路及海马神经元凋亡的影响。方法 75只大鼠根据随机数字法分为假手术组、模型组、阳性药物对照组（尼莫地平，8.0 mg/kg）、脑苷肌肽低剂量组（1.34 mg/kg）、脑苷肌肽高剂量组（2.68 mg/kg）。除假手术组外，其余各组大鼠建立缺氧缺血性脑损伤（HIBD）模型，分组给予相应药物处理后，进行Morris水迷宫实验，检测大鼠空间学习记忆能力；苏木精-伊红染色（HE）及原位细胞凋亡检测（TUNEL）法染色观察各组大鼠海马组织形态变化及神经元细胞凋亡情况；生化检测法测定大鼠海马组织中超氧化物歧化酶（SOD）、丙二醛（MDA）水平；Western blotting测定海马组织cGAS/STING通路蛋白表达水平。结果 与假手术组比较，模型组大鼠海马神经元细胞受损严重，大量神经元细胞发生凋亡，逃避潜伏期明显延长（P<0.05），穿越平台次数及SOD水平明显降低（P<0.05），MDA水平及cGAS、STING蛋白表达水平显著增加（P<0.05）；与模型组比较，阳性药尼莫地平组及脑苷肌肽低、高剂量组大鼠逃避潜伏期明显缩短（P<0.05），穿越平台次数明显增加（P<0.05），组织损伤程度降低，神经元凋亡数目明显减少，SOD水平显著升高（P<0.05），MDA水平、cGAS、STING蛋白表达量显著降低（P<0.05）。结论 脑苷肌肽可能通过抑制cGAS/STING信号通路，抑制氧化应激反应和海马区神经元细胞凋亡，减轻HIBD造成的大脑损伤，为临床上利用脑苷肌肽治疗HIE提供依据。

Objective To analyze the effects of cerebroside carnosine on cGAS/STING pathway and apoptosis of hippocampal neurons in neonatal rats with hypoxic-ischemic encephalopathy (HIE). Methods 75 rats were randomly divided into Sham operation group, model group, positive drug control group (nimodipine 8.0 mg/kg), cerebroside carnosine low-dose group (1.34 mg/kg) and cerebroside carnosine high-dose group (2.68 mg/kg). Except the Sham operation group, the rats in other groups were established hypoxic ischemic brain damage (HIBD) model, after treatment with corresponding drugs, Morris water maze test was carried out to test the spatial learning and memory ability of rats; Hematoxylin eosin staining (HE) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to observe the morphological changes of hippocampus and neuronal apoptosis; the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in hippocampus of rats were measured by biochemical method; the expression of cGAS/STING pathway protein in hippocampus was determined by Western blotting. Results Compared with the Sham operation group, the hippocampal neurons of rats in the model group were seriously damaged, a large number of neurons were apoptotic, and the escape latency was significantly prolonged (P<0.05), the number of crossing platform and SOD content were significantly decreased (P<0.05), MDA content and cGAS, STING protein expression levels were significantly increased (P<0.05). Compared with the model group, the escape latency of positive drug group, low-dose group and high-dose group was significantly shorter (P<0.05), the number of crossing platform was significantly increased (P<0.05), the degree of tissue damage was reduced, the number of neuronal apoptosis was significantly reduced, SOD content was significantly increased (P<0.05), MDA content and cGAS, STING content were significantly decreased (P<0.05). Conclusion Cerebroside carnosine may inhibit oxidative stress and apoptosis of hippocampal neurons by inhibiting cGAS/STING signaling pathway, and alleviate brain injury induced by HIE, and it has a more in-depth understanding of clinical application of cerebroside carnosine in the treatment of HIE.

R286.1