丙泊酚对胫骨骨折切开复位大鼠术后认知功能及cGAS/STING信号通路的影响
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河北省医学科学研究课题(20240954);


Effects of propofol on postoperative cognitive function and cGAS/STING signaling pathway in rats with tibial fractures undergoing open reduction
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    摘要:

    目的:探讨丙泊酚对胫骨骨折切开复位大鼠术后认知功能及cGAS/STING信号通路的影响。方法:将90只大鼠随机分为对照组、模型组、2′3′-cGAMP组、丙泊酚组和丙泊酚+2′3′-cGAMP组,每组各18只。除对照组外,其余各组麻醉期间均行胫骨骨折切开复位内固定手术。术后7 d,采用Y迷宫和新物体识别系统检测大鼠认知和记忆能力;采用Nissl染色评估海马组织CA1区神经元损伤;采用ELISA法测定海马组织中IL-18、TNF-α和IL-1β含量;采用RT-qPCR法测定海马组织中胆碱乙酰转移酶(ChAT)和γ-氨基丁酸A型受体α1(GABAARα1)mRNA相对表达量;采用Western blot测定海马组织中cGAS(环鸟苷酸-腺苷酸合成酶)、STING(干扰素基因刺激因子)、干扰素调节因子3(IRF3)、p-IRF3、NF-κB(核因子κB)p65和p-NF-κB p65蛋白相对表达量。结果:与对照组比较,模型组大鼠认知和记忆能力减弱(P<0.05),海马组织中CA1区神经元数量及ChAT和GABAARα1 mRNA相对表达量降低(P<0.05),IL-18、IL-1β、TNF-α和2′3′-cGAMP水平、cGAS和STING蛋白相对表达量及p-IRF3/IRF3和p-NF-κB p65/NF-κB p65比值升高(P<0.05);与模型组比较,2′3′-cGAMP组大鼠认知和记忆能力减弱(P<0.05),海马组织中CA1区神经元数量及ChAT和GABAARα1 mRNA相对表达量降低(P<0.05),IL-18、IL-1β、TNF-α和2′3′-cGAMP水平、cGAS和STING蛋白相对表达量及p-IRF3/IRF3和p-NF-κB p65/NF-κB p65比值升高(P<0.05);丙泊酚组上述指标结果均有改善(P<0.05),而2′3′-cGAMP可部分逆转丙泊酚的改善作用。结论:在胫骨骨折切开复位术后大鼠中,丙泊酚可通过抑制cGAS/STING信号通路活化,抗炎和保护神经,从而改善认知功能。

    Abstract:

    Objective: To explore the effect of propofol on cognitive dysfunction and cGAS/STING signaling pathway in rats with tibial fractures undergoing open reduction. Methods: 90 rats were randomly divided into control group, model group, 2'3'-cGAMP group, propofol group, and propofol + 2'3'-cGAMP group, with 18 rats in each group. Except for the control group, all other groups underwent open reduction and internal fixation surgery for tibial fractures during anaesthesia. At 7 d postoperatively, the recognition and memory function were evaluated through the Y Maze and new object recognition tests, the neuronal damage in CA1 region of hippocampus was evaluated through the Nissl staining, the IL-18, TNF-α and IL-1β levels in the hippocampal tissue were detected through the ELISA method, the choline acetyltransferase (ChAT) and γ-aminobutyric acid receptor Aα1 (GABAARα1) mRNA level in hippocampal tissue were detected through the RT-qPCR method, the cGAS (cyclic GMP-AMP synthetase), IRF (interferon regulatory factor) 3, p-IRF3, STING (stimulator of interferon genes), nuclear factor-κB (NF-κB) p65 and p-NF-κB p65 protein level in hippocampal tissue were detected through the Western blot method. Results: Compared with the control group, the model group rats exhibited decreased cognitive and memory abilities, along with a marked reduction in the number of neurons in the CA1 region of the hippocampal tissue, as well as decreased relative expression levels of ChAT and GABAARα1 mRNA. Additionally, there were increased levels of IL-18, IL-1β, TNF-α, and 2'3'-cGAMP, the relative expression levels of cGAS and STING proteins, and the ratios of p-IRF3/IRF3 and p-NF-κB p65/NF-κB p65 (P < 0.05). Compared with the model group, the 2'3'-cGAMP group rats also displayed decreased cognitive and memory abilities, a marked reduction in the number of neurons in the CA1 region of the hippocampal tissue, and decreased relative expression levels of ChAT and GABAARα1 mRNA. Furthermore, there were increased levels of IL-18, IL-1β, TNF-α, and 2'3'-cGAMP, the relative expression levels of cGAS and STING proteins, and the ratios of p-IRF3/IRF3 and p-NF-κB p65/NF-κB p65 (P < 0.05). The above-mentioned indicators showed improvement in the propofol group, while 2'3'-cGAMP partially reversed the ameliorative effects of propofol. Conclusion: In rats after tibial fracture open reduction, propofol can improve cognitive function by inhibiting the activation of cGAS/STING signaling pathway for anti-inflammatory and nerve protection. 如需进一步润色、翻译或格式化为学术论文段落,也可以告诉我!

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底妍;王金保;焦姗姗;李晓聪;李红霞;郝书航;.丙泊酚对胫骨骨折切开复位大鼠术后认知功能及cGAS/STING信号通路的影响[J].川北医学院学报,2025,40(12):1497-1502.

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  • 在线发布日期: 2026-01-07
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