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香椿籽油多酚通过抑制 p38 MAPK 信号通路缓解帕金森病大鼠模型中 6-羟多巴胺诱导的神经炎症。

Polyphenols from Toona sinensiss Seeds Alleviate Neuroinflammation Induced by 6-Hydroxydopamine Through Suppressing p38 MAPK Signaling Pathway in a Rat Model of Parkinson's Disease.

机构信息

Center for Experimental Medical Research, Weifang Medical University, Weifang, 261053, Shandong, China.

Department of Histology and Embryology, Weifang Medical University, Weifang, 261053, Shandong, China.

出版信息

Neurochem Res. 2020 Sep;45(9):2052-2064. doi: 10.1007/s11064-020-03067-2. Epub 2020 Jun 17.

DOI:10.1007/s11064-020-03067-2
PMID:32556929
Abstract

Polyphenols from Toona sinensis seeds (PTSS) have demonstrated anti-inflammatory effects in various diseases, while the anti-neuroinflammatory effects still remain to be investigated. We aimed to investigate the effects of PTSS on Parkinson's disease and underlying mechanisms using a rat model. We employed 6-hydroxydopamine (6-OHDA) to male Sprague Dawley (SD) rats and PC12 cells to construct the in vivo and vitro models of PD and dopaminergic (DA) neuron injury, respectively. Cell viability was detected by cell counting kit-8 (CCK-8) assay and protein levels of inflammatory mediators and some p38 MAPK pathway molecules were investigated by immunohistochemistry and Western blot analyses. The results showed that 6-OHDA significantly increased protein levels of inflammatory mediators, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and tumor necrosis factor α (TNF-α), which could be reversed by PTSS through suppressing the p38 MAPK pathway. The anti-inflammatory effects of PTSS were significantly enhanced by the specific p38 inhibitor of SB203580 in vitro. The present work suggests that PTSS can exert anti-inflammatory effects on PD models, which may be attributed to the suppression of p38 MAPK signaling pathway.

摘要

香椿籽多酚(PTSS)已在多种疾病中表现出抗炎作用,但其抗神经炎症作用仍有待研究。我们旨在使用大鼠模型研究 PTSS 对帕金森病的影响及其作用机制。我们使用 6-羟多巴胺(6-OHDA)构建雄性 Sprague Dawley(SD)大鼠体内和 PC12 细胞体外帕金森病和多巴胺能(DA)神经元损伤模型,分别通过细胞计数试剂盒(CCK-8)测定细胞活力,通过免疫组化和 Western blot 分析测定炎症介质和一些 p38 MAPK 通路分子的蛋白水平。结果表明,6-OHDA 可显著增加炎症介质的蛋白水平,如环加氧酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)和肿瘤坏死因子-α(TNF-α),PTSS 可通过抑制 p38 MAPK 通路来逆转这种情况。在体外,p38 MAPK 的特异性抑制剂 SB203580 显著增强了 PTSS 的抗炎作用。本研究表明,PTSS 对 PD 模型具有抗炎作用,这可能归因于抑制 p38 MAPK 信号通路。

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