摘要
目的 探讨mir-325-3p通过调控RIPK3/TFEB通路对脑出血大鼠神经元损伤的影响。 方法 雄性SD大鼠随机分为假手术组、脑出血组、agomir NC组、agomir-325-3p组、GSK872(RIPK3抑制剂)组、agomir-325-3p+GSK872组,每组18只。评估大鼠运动功能、肢体协调能力、改良神经功能缺损评分(mNSS),测定大鼠脑含水量、血肿周围脑组织病理变化、神经细胞凋亡、神经元自噬、LC3与NeuN共定位、海马组织RIPK3/TFEB信号通路、自噬相关蛋白表达。 结果 与假手术组相比,脑出血组CA1区神经元肿胀,排列疏松,可见大量溶酶体和自噬小体,前肢放置成功率、左侧转身百分比、TFEB下降(P<0.05),mNSS评分、脑含水量、神经细胞凋亡率、RIPK3、Beclin-1和LC3-II/LC3-Ⅰ、LC3/NeuN强阳性个数升高(P<0.05);agomir-325-3p、GSK872可减轻大鼠海马神经元损伤,增强自噬,且两者有协同作用。 结论 mir-325-3p过表达可通过调控RIPK3/TFEB促进自噬,减轻脑出血大鼠神经元损伤。
Abstract
Objective To investigate the effect of mir-325-3p on neuronal injury in rats with intracerebral hemorrhage by regulating RIPK3/TFEB pathway. Methods SD male rats were randomly divided into a sham operation group, an intracerebral hemorrhage group, an agomir NC group, an agomir-325-3p group, a GSK872 (RIPK3 inhibitor) group, and an agomir-325-3p+GSK872 group, with 18 rats in each group. The motor function, limb coordination ability and modified neurological deficit score (MNSs) of rats were evaluated. The brain water content, pathological changes of brain tissue around hematoma, neuronal apoptosis, autophagy of rats, CO localization of LC3 and NeuN, RIPK3/TFEB signal pathway in hippocampus and the expression of autophagy related proteins were measured. Results Compared with the sham operation group, the neurons in CA1 area of intracerebral hemorrhage group were swollen and loosely arranged, with a large number of lysosomes and autophagy bodies, the success rate of forelimb placement, the percentage of left turn and TFEB decreased (P<0.05), and the MNSs score, brain water content, the rate of neuronal apoptosis, RIPK 3, Beclin-1, LC3-II / LC3 - Ⅰ and LC3 / NeuN strong positive numbers increased (P<0.05). Agomir-325-3p and GSK872 can reduce the damage of hippocampal neurons and enhance autophagy. Conclusions Mir-325-3p overexpression may promote autophagy and reduce neuronal damage in rats with intracerebral hemorrhage by regulating RIPK3 / TFEB.
关键词
mir-325-3p;  /
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RIPK3/TFEB;  /
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脑出血;  /
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神经元损伤
Key words
mir-325-3p;  /
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RIPK3/TFEB;  /
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cerebral hemorrhage;  /
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neuronal damage
马晓维, 周喜燕, 李彬, 臧运华, 王群, 于淼.
mir-325-3p激活RIPK3/TFEB信号通路减轻脑出血大鼠神经元损伤[J]. 中国临床解剖学杂志. 2023, 41(4): 422-427 https://doi.org/10.13418/j.issn.1001-165x.2023.4.09
Ma Xiaowei, Zhou Xiyan, Li Bin, Zang Yunhua, Wang Qun, Yu Miao.
Mir-325-3p attenuates neuronal injury in rats with intracerebral hemorrhage by activating RIPK33 / TFEB signaling pathway[J]. Chinese Journal of Clinical Anatomy. 2023, 41(4): 422-427 https://doi.org/10.13418/j.issn.1001-165x.2023.4.09
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基金
山东中医药科技发展计划项目(2015-356)