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马钱子苷通过JAK2/STAT3信号通路减轻脑缺血再灌注损伤中的炎症、氧化应激和细胞凋亡。

Loganin attenuates the inflammation, oxidative stress, and apoptosis through the JAK2/STAT3 pathway in cerebral ischemia-reperfusion injury.

作者信息

Xi Yunfeng, Hou Xiaoli, Huang Yuan, Zhou Yan, Chen Yu, Wang Yixia, Cheng Hong

机构信息

Yangzhou University Medical College; Nanjing Luhe people's Hospital, Yangzhou University, Yangzhou 22500, Jiangsu Province, China.

Yangzhou University Medical College; Nanjing Luhe people's Hospital, Yangzhou University, Yangzhou 22500, Jiangsu Province, China; Department of Medical Science, Yangzhou Polytechnic College, Yangzhou 22500, Jiangsu Province, China.

出版信息

J Stroke Cerebrovasc Dis. 2025 Jan;34(1):108114. doi: 10.1016/j.jstrokecerebrovasdis.2024.108114. Epub 2024 Nov 12.

DOI:10.1016/j.jstrokecerebrovasdis.2024.108114
PMID:39537043
Abstract

Loganin, a monoterpene iridoid glycoside derived from Cornus officinalis Sieb. Et Zucc, has been reported to have anti-inflammatory and antioxidant activity. Nevertheless, the potential role and molecular mechanism of loganin in cerebral ischemia-reperfusion (I/R) injury are not well-understood. The purpose of the study was to explore the functional role of loganin in the inflammation, oxidative stress, and apoptosis in cerebral I/R injury in rats MATERIALS AND METHODS: Following middle cerebral artery occlusion (MCAO), 80 mg/kg of loganin was intragastrically administered for 7 consecutive days. Neuromotor function scores were performed 24 h after the last administration, and the cerebral infarction volume was determined by TTC straining. The expressions of IL-6, IL-1β, and TNF-α in the brain tissues of MCAO rats were detected by ELISA assay. The activities of ROS, SOD, and MDA were measured by ELISA assay as well. Cell apoptosis were was tested by TUNEL straining. Western blot assay was applied for measuring the protein levels RESULTS: We observed that the expressions of IL-6, IL-1β, and TNF-α were amplitude markedly elevated in the rats following MCAO. Treatment with loganin obviously reduced these expressions in the brain tissues of MCAO rats. ELISA assay showed that ROS generation and MDA activity were increased in MCAO group and it was decreased after treatment with loganin. However, loganin increased the SOD activity, which was reduced by MCAO operation. Moreover, loganin promoted neurological function improvement and inhibited cell apoptosis in the rats after MCAO. Mechanically, loganin triggered JAK2/STAT3 phosphorylation in the rats following MCAO, and activation of JAK2/STAT3 pathway rescued the inhibition effects of loganin on the inflammation, oxidative stress, and apoptosis CONCLUSIONS: These results provide evidence that loganin may alleviate the inflammation, oxidative stress, and apoptosis through the JAK2/STAT3 pathway in MCAO rats.

摘要

马钱苷是一种从山茱萸中提取的单萜环烯醚萜苷,据报道具有抗炎和抗氧化活性。然而,马钱苷在脑缺血再灌注(I/R)损伤中的潜在作用和分子机制尚不清楚。本研究的目的是探讨马钱苷在大鼠脑I/R损伤中的炎症、氧化应激和细胞凋亡中的功能作用。材料与方法:大脑中动脉闭塞(MCAO)后,连续7天胃内给予80mg/kg马钱苷。末次给药24小时后进行神经运动功能评分,通过TTC染色测定脑梗死体积。采用ELISA法检测MCAO大鼠脑组织中IL-6、IL-1β和TNF-α的表达。同时采用ELISA法检测ROS、SOD和MDA的活性。通过TUNEL染色检测细胞凋亡。采用蛋白质免疫印迹法检测蛋白质水平。结果:我们观察到MCAO后大鼠IL-6、IL-1β和TNF-α的表达明显升高。马钱苷治疗明显降低了MCAO大鼠脑组织中的这些表达。ELISA分析表明,MCAO组ROS生成和MDA活性增加,马钱苷治疗后降低。然而,马钱苷增加了SOD活性,而MCAO手术使其降低。此外,马钱苷促进了MCAO后大鼠神经功能的改善并抑制了细胞凋亡。机制上,马钱苷在MCAO后大鼠中触发JAK2/STAT3磷酸化,JAK2/STAT3通路的激活挽救了马钱苷对炎症、氧化应激和细胞凋亡的抑制作用。结论:这些结果提供了证据,表明马钱苷可能通过JAK2/STAT3通路减轻MCAO大鼠的炎症、氧化应激和细胞凋亡。

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