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

作　　者：冯松林 张涛 冯凌 胡超 杨远波 邓琳 邓大炜 兰宗婷 FENG Songlin;ZHANG Tao;FENG Ling;HU Chao;YANG Yuanbo;DENG Lin;DENG Dawei;LAN Zongting(Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China;Department of Orthopedics,Nanchong Central Hospital,Nanchong 637000,China)

机构地区：[1]川北医学临床医学院附属医院,南充637000 [2]南充市中心医院骨科,南充637000

出　　处：《世界中医药》2025年第2期216-222,共7页World Chinese Medicine

基　　金：国家自然科学基金项目(82300737);四川省医学会科研课题(S21059)。

摘　　要：目的:探讨木犀草素(Lut)调节生长停滞特异基因6(GAS6)/AXL受体型酪氨酸激酶(AXL)信号通路对金黄色葡萄球菌(金葡菌)颅内感染大鼠血脑屏障(BBB)功能障碍的治疗作用及机制。方法:取SD大鼠通过颅内注射金葡菌菌液的方法建立颅内感染模型,以随机数表法随机分为模型组(M组)、木犀草素低剂量组(Lut-L组)、木犀草素高剂量组(Lut-H组)、空载质粒组(pc-NC组)、木犀草素高剂量+si-GAS6组(Lut-H+si-GAS6组),设颅内注射等量生理盐水的SD大鼠为假手术组(Sh组)。造模后24 h,Lut-L组、Lut-H组大鼠分别经腹腔注射1.4 mg/mL、2.8 mg/mL的Lut溶液,同时经尾静脉注射与Lut-H+si-GAS6组等剂量的生理盐水;pc-NC组大鼠经腹腔注射生理盐水,同时经尾静脉注射空载质粒;Lut-H+si-GAS6组大鼠经腹腔注射2.8 mg/mL的Lut溶液,同时经尾静脉注射GAS6 siRNA质粒;M组、Sh组大鼠经腹腔注射生理盐水,同时经尾静脉注射与Lut-H+si-GAS6组等剂量的生理盐水。各组大鼠均干预2周。检测大鼠改良神经功能缺损评分(mNSS)、BBB通透性、脑组织BBB紧密连接相关蛋白表达、脑组织细胞凋亡率与线粒体膜电位(MMP)、脑组织炎症介质水平与GAS6/AXL信号蛋白表达。结果:与Sh组比较,M组mNSS、伊文思蓝(EB)含量、脑组织细胞凋亡率、脑组织白细胞介素-1β(IL-1β)、IL-6、IL-18与IL-17水平高(P<0.05),脑组织闭锁小带蛋白1(ZO-1)与紧密连接蛋白5(Claudin-5)表达、脑组织细胞MMP、脑组织GAS6与AXL蛋白表达低(P<0.05);与M组比较,Lut-L组、Lut-H组mNSS、EB含量、脑组织细胞凋亡率、脑组织IL-1β、IL-6、IL-18与IL-17水平低(P<0.05),脑组织ZO-1与Claudin-5表达、脑组织细胞MMP、脑组织GAS6与AXL蛋白表达高(P<0.05),Lut-H组以上指标变化更明显(P<0.05),pc-NC组以上指标无明显变化(P>0.05);Lut-H+si-GAS6组大鼠以上指标与Lut-H组比较差异有统计学意义(P<0.05)。结论:Lut可通过激活GAS6/AXL信号通路抑制金�Objective:To investigate the therapeutic effects and mechanisms of luteolin(Lut)in regulating the growth arrest-specific gene 6(GAS6)/AXL receptor tyrosine kinase signaling pathway on blood-brain barrier(BBB)dysfunction in rats with intracranial infection of Staphylococcus aureus.Methods:Sprague-Dawley(SD)rats were subjected to intracranial injection of S.aureus to establish 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 volume 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 equivalent 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-1β),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 tissu

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 

分 类 号：R285.5[医药卫生—中药学]