摘要
目的:探讨麝香酮对缺血性脑卒中(IS)大鼠神经炎症的影响及其作用机制。方法:将SD大鼠随机分为对照组、大脑中动脉闭塞(MCAO)组、MCAO+cGAS抑制剂(RU.521)组、麝香酮组、麝香酮+STING激动剂(2′3′-cGAMP)组,每组10只。采用MCAO法构建IS大鼠模型,对各组大鼠进行神经功能缺损评分,TTC染色检测脑梗死面积,HE染色和Nissl染色观察神经元病理变化和损伤,TUNEL法检测神经元凋亡,ELISA法检测IL-6、IL-1β、TNF-α水平,Western blotting法检测cGAS-STING信号通路蛋白表达。结果:与对照组比较,MCAO组大鼠海马组织神经元细胞皱缩,Nissl体减少,神经功能缺损评分、脑梗死面积、神经元凋亡率、IL-6水平、IL-1β水平、TNF-α水平,以及IL-1β、TNF-α、cGAS、STING、p-IRF3蛋白表达均显著升高(P<0.05);与MCAO组比较,MCAO+RU.521组、麝香酮组大鼠海马组织神经元病理损伤减轻,Nissl体增加,神经功能缺损评分、脑梗死面积、神经元凋亡率、IL-6水平、IL-1β水平、TNF-α水平,以及IL-1β、TNF-α、cGAS、STING、p-IRF3蛋白表达均显著降低(P<0.05);STING激动剂可逆转麝香酮对IS大鼠海马组织神经元细胞损伤和神经炎症的改善作用(P<0.05)。结论:麝香酮可能通过抑制cGAS-STING信号通路激活,减少IS大鼠神经元损伤,改善神经炎症。
Objective:To investigate the impact and mechanism of muscone on neuroinflammation in ischemic stroke(IS)rats.Methods:SD rats were randomly grouped into control group,MCAO group,MCAO+cGAS inhibitor(RU.521)group,muscone group and muscone+STING agonist(2′3′-cGAMP)group,10 rats in each group.IS rat model was constructed using the MCAO method.The neurological deficits of rats in each group were scored,and TTC staining was applied to detect the area of cerebral infarction.HE staining and Nissl staining were applied to observe the pathological changes and damage of neurons.TUNEL method was applied to detect neuronal apoptosis.ELISA method was applied to detect the levels of IL-6,IL-1βand TNF-α.Western blotting was applied to detect the expression of cGAS-STING signaling pathway proteins.Results:Compared with control group,the neuronal cells in the hippocampus shrank and Nissl bodies decreased in MCAO group.And the neurological deficit score,cerebral infarction area,neuronal apoptosis rate,the levels of IL-6,IL-1βand TNF-α,and the expression of IL-1β,TNF-α,cGAS,STING and p-IRF3 proteins were obviously increased in MCAO group(P<0.05).Compared with MCAO group,the pathological damage of hippocampal neurons was reduced in MCAO+RU.521 group and muscone group,while Nissl bodies increased in MCAO+RU.521 group and muscone group.And the neurological deficit score,cerebral infarction area,neuronal apoptosis rate,the levels of IL-6,IL-1βand TNF-α,and the expression of IL-1β,TNF-α,cGAS,STING and p-IRF3 proteins were obviously reduced in MCAO+RU.521 group and muscone group(P<0.05).STING agonists was able to reverse the improvement effects of muscone on neuronal cell damage and neuroinflammation in the hippocampus of IS rats(P<0.05).Conclusion:Muscone may reduce neuronal damage and improve neuroinflammation in IS rats by inhibiting the activation of the cGAS-STING signaling pathway.
作者
刚瑛
丁鹏
李冰
张文想
GANG Ying;DING Peng;LI Bing;ZHANG Wenxiang(Dongzhimen Hospital,Beijing University of Traditional Chinese Medicine,Beijing 100700,China)
出处
《中医药导报》
2024年第3期20-24,42,共6页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
中华中医药学会委托课题项目(2021XS-001-06)。
