目的 分析腦苷肌肽對缺氧缺血性腦?。℉IE）新生大鼠環(huán)磷酸鳥苷-腺苷合成酶（cGAS）/膜蛋白干擾素基因刺激因子（STING）通路及海馬神經(jīng)元凋亡的影響。方法 75只大鼠根據(jù)隨機(jī)數(shù)字法分為假手術(shù)組、模型組、陽性藥物對照組（尼莫地平，8.0 mg/kg）、腦苷肌肽低劑量組（1.34 mg/kg）、腦苷肌肽高劑量組（2.68 mg/kg）。除假手術(shù)組外，其余各組大鼠建立缺氧缺血性腦損傷（HIBD）模型，分組給予相應(yīng)藥物處理后，進(jìn)行Morris水迷宮實(shí)驗(yàn)，檢測大鼠空間學(xué)習(xí)記憶能力；蘇木精-伊紅染色（HE）及原位細(xì)胞凋亡檢測（TUNEL）法染色觀察各組大鼠海馬組織形態(tài)變化及神經(jīng)元細(xì)胞凋亡情況；生化檢測法測定大鼠海馬組織中超氧化物歧化酶（SOD）、丙二醛（MDA）水平；Western blotting測定海馬組織cGAS/STING通路蛋白表達(dá)水平。結(jié)果 與假手術(shù)組比較，模型組大鼠海馬神經(jīng)元細(xì)胞受損嚴(yán)重，大量神經(jīng)元細(xì)胞發(fā)生凋亡，逃避潛伏期明顯延長（P<0.05），穿越平臺次數(shù)及SOD水平明顯降低（P<0.05），MDA水平及cGAS、STING蛋白表達(dá)水平顯著增加（P<0.05）；與模型組比較，陽性藥尼莫地平組及腦苷肌肽低、高劑量組大鼠逃避潛伏期明顯縮短（P<0.05），穿越平臺次數(shù)明顯增加（P<0.05），組織損傷程度降低，神經(jīng)元凋亡數(shù)目明顯減少，SOD水平顯著升高（P<0.05），MDA水平、cGAS、STING蛋白表達(dá)量顯著降低（P<0.05）。結(jié)論 腦苷肌肽可能通過抑制cGAS/STING信號通路，抑制氧化應(yīng)激反應(yīng)和海馬區(qū)神經(jīng)元細(xì)胞凋亡，減輕HIBD造成的大腦損傷，為臨床上利用腦苷肌肽治療HIE提供依據(jù)。

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.

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