线粒体自噬-NLRP3炎症小体通路在新生大鼠缺血性 脑损伤中的作用研究. (Chinese)
In: Tianjin Medical Journal, Jg. 51 (2023-11-01), Heft 11, S. 1181-1186
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Zugriff:
Objective To investigate the effect of mitophagy-NOD-like receptor heat protein domain associated protein 3 (NLRP3) inflammasome pathway on cerebral ischemic injury in neonatal rats. Methods Forty-two 7-day SD rats were divided into the sham group, the cerebral ischemia-reperfusion injury (CIRI) group, the CIRI+dimethyl sulfoxide (DMSO) group, the CIRI+Mdivi-1 group, the CIRI+MCC950 group and the CIRI+Ac-YVAD-CMK group (7 rats in each group). Except for the sham group, the neonatal rat model of hypoxic-ischemic brain injury was established by unilateral common carotid artery occlusion. Neurological symptom score was performed by Londa method. Cell morphology in CA1 region of hippocampus was observed by hematoxylin-eosin (HE) staining. Ultrastructure of hippocampal neurons was observed by transmission electron microscopy, and related proteins of mitochondrial autophagy and NLRP3 inflammasome pathway were detected by Western blot assay. Results Compared with the CIRI+DMSO group, the CIRI+Mdivi-1 group had higher scores of neurobehavioral disorders, fewer synapses and more swollen mitochondria (all P<0.05). Compared with the CIRI+Mdivi-1 group, the neurobehavioral disorder score and the number of synapses increased, and the number of swollen mitochondria decreased in the CIRI+MCC950 group and the CIRI+Ac-YVAD-cmk group (all P<0.05). Compared with the CIRI+DMSO group, the protein expressions of PINK1, Parkin and LC3 Ⅱ/Ⅰ were down-regulated in the CIRI+ Mdivi-1 group, and the protein expressions of TOMM20, P62, NLRP3, caspase-1 and caspase-8 were up-regulated (P< 0.05). Compared with the CIRI+Mdivi-1 group, the protein expressions of PINK1, Parkin, LC3 Ⅱ/Ⅰ were up-regulated in the CIRI+MCC950 group and the CIRI+Ac-YVAD-cmk group (P<0.05). The expression levels of NLRP3, caspase-1 and caspase-8 proteins were down-regulated in the CIRI+MCC950 group, and caspase-1 and caspase-8 proteins decreased in the CIRI+Ac-YVAD-cmk group (P<0.05). Conclusion Activation of mitochondrial autophagy or inhibition of NLRP3 inflammasome activation have protective effects on cerebral ischemic injury in neonatal rats. [ABSTRACT FROM AUTHOR]
目的 探讨线粒体自噬-NOD样受体热蛋白结构域相关蛋白3 (NLRP3)炎症小体通路对新生大鼠缺血性 脑损伤的影响。方法 将42只1周龄SD大鼠分为Sham组、脑缺血-再灌注损伤 (CIRI)组、CIRI+二甲基亚砜 (DMSO) 组、CIRI+Mdivi-1组、CIRI+MCC950组、CIRI+Ac-YVAD-cmk组,每组7只。除Sham组外,其他各组采用单侧颈总动 脉阻断法建立新生大鼠缺氧缺血性脑损伤模型。采用Londa法行神经行为障碍评分,HE染色观察海马体CA1区细 胞形态,透射电子显微镜观察海马神经元超微结构,Western blot检测线粒体自噬和NLRP3炎症小体通路相关蛋白。 结果 与CIRI+DMSO组比较,CIRI+Mdivi-1组的神经行为障碍评分增加,突触数减少及肿胀线粒体数增多 (均P< 0.05);与CIRI+Mdivi-1组比较,CIRI+MCC950组及CIRI+Ac-YVAD-cmk组神经行为障碍评分降低,突触数增多及肿 胀线粒体数减少 (均P<0.05)。与CIRI+DMSO组比较,CIRI+Mdivi-1组PTEN诱导的激酶1 (PINK1)、Parkin、LC3Ⅱ/ Ⅰ表达下调,线粒体外膜转位酶20 (TOMM20)、P62及NLRP3、胱天蛋白酶 (caspase)-1、caspase-8蛋白表达增加 (P< 0.05)。与CIRI+Mdivi-1组比较,CIRI+MCC950组及CIRI+Ac-YVAD-cmk 组PINK1、Parkin、LC3Ⅱ/Ⅰ蛋白表达增加 (P<0.05),CIRI+MCC950 组 NLRP3、caspase-1、caspase-8 蛋白及 CIRI+Ac-YVAD-cmk 组 caspase-1、caspase-8 蛋白 表达下调。结论 激活线粒体自噬或抑制NLRP3炎症小体活化对新生大鼠缺血性脑损伤具有保护作用。 [ABSTRACT FROM AUTHOR]
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Titel: |
线粒体自噬-NLRP3炎症小体通路在新生大鼠缺血性 脑损伤中的作用研究. (Chinese)
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Autor/in / Beteiligte Person: | 林永文 ; 陈巧媚 ; 敖当 ; 黄炳龙 ; 骆成珠 ; 李承燕 |
Link: | |
Zeitschrift: | Tianjin Medical Journal, Jg. 51 (2023-11-01), Heft 11, S. 1181-1186 |
Veröffentlichung: | 2023 |
Medientyp: | academicJournal |
ISSN: | 0253-9896 (print) |
DOI: | 10.11958/20230415 |
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