世界中医药2025，Vol.20Issue(2)：216-222,7.DOI:10.3969/j.issn.1673-7202.2025.02.005
木犀草素对金葡菌颅内感染大鼠血脑屏障功能障碍的治疗作用及机制
Effects and Mechanisms of Luteolin in Treatment of Blood-brain Barrier Dysfunction in Rats with Intracranial Infection of Staphylococcus aureus
摘要
Abstract
Objective:To investigate the therapeutic effects and mechanisms of luteolin(Lut)in regulating the growth arrest-specif-ic gene 6(GAS6)/AXL receptor tyrosine kinase signaling pathway on blood-brain barrier(BBB)dysfunction in rats with intracrani-al infection of Staphylococcus aureus.Methods:Sprague-Dawley(SD)rats were subjected to intracranial injection of S.aureus to es-tablish an intracranial infection model and the model rats were randomly assigned into the model group(M group),low-dose Lut group(Lut-L group),high-dose Lut group(Lut-H group),empty vector group(pc-NC group),and high-dose Lut combined with si-GAS6 group(Lut-H+si-GAS6 group).A sham-operated group(Sh group)was included,in which rats received an equivalent vol-ume of normal saline instead of S.aureus.At 24 hours post-modeling,rats in the Lut-L and Lut-H groups received intraperitoneal injections of 1.4 mg/mL and 2.8 mg/mL Lut solution,respectively,along with tail vein injections of normal saline in doses equiva-lent to those in the Lut-H+si-GAS6 group.The pc-NC group received intraperitoneal saline injections and tail vein injections of an empty vector plasmid.The Lut-H+si-GAS6 group received intraperitoneal injections of 2.8 mg/mL Lut solution along with tail vein injections of GAS6 siRNA plasmid.The M and Sh groups received intraperitoneal and tail vein injections of normal saline in the same doses as the Lut-H+si-GAS6 group.All groups were treated for two weeks.The modified neurological severity score(mNSS),BBB permeability,expression of tight junction proteins in brain tissue,neuronal apoptosis rate,mitochondrial membrane potential(MMP),levels of pro-inflammatory cytokines,and expression of GAS6/AXL signaling proteins were assessed.Results:Compared with the Sh group,the M group showed significantly higher mNSS,Evans blue(EB)content,neuronal apoptosis rate,and levels of interleukin-1β(IL-1 β),IL-6,IL-18,and IL-17 in brain tissue(P＜0.05),while the expression of zonula occludens-1(ZO-1)and claudin-5,MMP,and GAS6 and AXL expression levels in brain tissue were significantly lower(P＜0.05).Compared with the M group,the Lut-L and Lut-H groups exhibited lower mNSS,EB content,neuronal apoptosis rate,and IL-1 β,IL-6,IL-18,and IL-17 levels(P＜0.05),along with higher ZO-1 and claudin-5 expression,MMP,and GAS6 and AXL protein levels(P＜0.05).These effects were more pronounced in the Lut-H group(P＜0.05).The pc-NC group showed no significant changes(P＞0.05).Com-pared with the Lut-H group,the Lut-H+si-GAS6 group exhibited significant differences in the above indices(P＜0.05).Conclu-sion:Lut alleviates BBB dysfunction and neurological impairment in rats with S.aureus-induced intracranial infection by activating the GAS6/AXL signaling pathway,thereby suppressing neuroinflammation and reducing neuronal apoptosis.关键词
木犀草素/生长停滞特异基因6/AXL受体型酪氨酸激酶信号通路/金黄色葡萄球菌/颅内感染/血脑屏障/作用机制/神经功能损伤/大鼠Key words
Luteolin/Growth arrest-specific gene 6(GAS6)/AXL receptor tyrosine kinase signaling pathway/Staphylococcus au-reus/Intracranial infection/Blood-brain barrier/Mechanism of action/Neurological function impairment/Rat分类
医药卫生引用本文复制引用
冯松林,张涛,冯凌,胡超,杨远波,邓琳,邓大炜,兰宗婷..木犀草素对金葡菌颅内感染大鼠血脑屏障功能障碍的治疗作用及机制[J].世界中医药,2025,20(2):216-222,7.基金项目
国家自然科学基金项目(82300737) （82300737）
四川省医学会科研课题(S21059) （S21059）
