Effect and mechanism of luteolin on brain injury in rats with hypoxia-ischemia encephalopathy
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 33, Issue 12, Pages: 1033-1038(2024)
- 作者机构：
武汉市中医医院脑病科，湖北 武汉 430014
- 作者简介：
- 基金信息：
DOI：10.11659/jjssx.12E023050
CLC： R722.1Published：25 December 2024，
Received：13 December 2023，
- 稿件说明：
移动端阅览
杨畅,金海涛,张雯.木犀草苷对缺氧缺血性脑病大鼠脑损伤的影响及机制[J].局解手术学杂志,2024,33(12):1033-1038.
YANG Chang,JIN Hai-tao,ZHANG Wen.Effect and mechanism of luteolin on brain injury in rats with hypoxia-ischemia encephalopathy[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(12):1033-1038.
杨畅,金海涛,张雯.木犀草苷对缺氧缺血性脑病大鼠脑损伤的影响及机制[J].局解手术学杂志,2024,33(12):1033-1038. DOI： 10.11659/jjssx.12E023050.
YANG Chang,JIN Hai-tao,ZHANG Wen.Effect and mechanism of luteolin on brain injury in rats with hypoxia-ischemia encephalopathy[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(12):1033-1038. DOI： 10.11659/jjssx.12E023050.
摘要
目的
2
探讨木犀草苷对缺氧缺血性脑病（HIE）大鼠脑损伤和Toll样受体4（TLR4）/核因子-κB（NF-κB）信号通路的影响。
方法
2
将60只雄性大鼠随机分为正常对照（NC）组、模型组、低剂量组（25 mg/kg木犀草苷）、高剂量组（50 mg/kg木犀草苷）、高剂量+脂多糖（LPS）组（50 mg/kg木犀草苷+0.5 mg/kg TLR4激动剂LPS），每组12只。用颈总动脉结扎及缺氧手段构建HIE模型。采用神经功能缺损评分（NSS）检测各组大鼠脑部神经功能；ELISA法测量血清肿瘤坏死因子-α（TNF-α）、脑源性神经营养因子（BDNF）水平；HE染色检测脑组织病理变化；试剂盒测定大鼠脑组织丙二醛（MDA）、超氧化物歧化酶（SOD）水平；TTC染色检测大鼠脑梗死情况；Western blot检测脑组织TLR4、核因子-κB（NF-κB）、p-NF-κB、活化的半胱氨酸天冬氨酸蛋白酶3（Cleaved Caspase-3）蛋白表达。
结果
2
与模型组比较，低剂量组、高剂量组大鼠NSS，TNF-α、MDA水平，脑梗死体积及TLR4、p-NF-κB/NF-κB、Cleaved Caspase-3表达降低/减少（
P
<
0.05），BDNF、SOD水平升高（
P
<
0.05），海马区组织病理损伤明显减轻，结构逐渐清晰，神经细胞数量正常；与高剂量组比较，高剂量+LPS组上述指标水平均相反表达（
P
<
0.05），海马区组织病理损伤加重。
结论
2
木犀草苷可改善HIE大鼠脑损伤并抑制TLR4/NF-κB信号通路，且TLR4/NF-κB信号通路的抑制可能是木犀草苷改善脑损伤的作用机制。
Abstract
Objective
2
To investigate the effects of luteolin on brain injury and Toll like receptor 4 （TLR4）/nuclear factor-kappa B （NF-κB） signaling pathway in rats with hypoxia-ischemia encephalopathy （HIE）.
Methods
2
A total of 60 male rats were randomly divided into the normal control （NC） group， the model group， the low-dose group （25 mg/kg luteolin）， the high-dose group （50 mg/kg luteolin）， and the high-dose+lipopolysaccharide （LPS） group （50 mg/kg luteolin+0.5 mg/kg TLR4 agonist LPS）， with 12 rats in each group. HIE model was constructed by ligation of common carotid artery and hypoxia. Neurological severity score （NSS） was used to detect the cerebral nerve function of rats in each group. Serum tumor necrosis factor-α （TNF-α） and brain-derived neurotrophic factor （BDNF） levels were detected by ELISA assay. HE staining was used to detect the pathological changes of brain tissue. The levels of malondialdehyde （MDA） and superoxide dismutase （SOD） in brain tissue of rats were detected by kit. TTC staining was used to detect cerebral infarction in rats. Western blot was used to detect the expression of TLR4， nuclear factor-kappa B （NF-κB）， p-NF-κB， activated cleaved cysteine aspartate proteinase 3 （Cleaved Caspase-3） protein in brain tissue.
Results
2
Compared with the model group， the NSS，levels of TNF-α and MDA， volume of cerebral infarction， and expression of TLR4， p-NF-κB/NF-κB and Cleaved Caspase-3 in low-dose group and high-dose group were decreased （
P
<
0.05）， BDNF and SOD levels were increased （
P
<
0.05）， the histopathological damage of hippocampus was obviously alleviated， the structure was gradually clear， and the number of nerve cells was normal. Compared with the high-dose group， the levels of the above indexes were inversely expressed in the high-dose+LPS group （
P
<
0.05）， and the histopathological damage in the hippocampus was aggravated.
Conclusion
2
Luteolin can improve brain injury and inhibit TLR4/NF-κB signaling pathway in HIE rats， and the inhibition of TLR4/NF-κB signaling pathway may be the mechanism of luteolin in improving brain injury.
关键词
木犀草苷Toll样受体4核因子-κB缺氧缺血性脑病
Keywords
luteolinToll-like receptor 4nuclear factor-kappa Bhypoxia-ischemia encephalopathy
references
Bonifacio SL，Hutson S.The term newborn：evaluation for hypoxic-ischemic encephalopathy［J］.Clin Perinatol，2021，48（3）：681-695.doi：10.1016/j.clp.2021.05.014http://dx.doi.org/10.1016/j.clp.2021.05.014.
Papazian O.Neonatal hypoxic-ischemic encephalopathy［J］.Medicina （B Aires），2018，78（2）：36-41.
赵孟，王玉婷，戢汉斌.金银花木樨草苷对大鼠抑郁及中枢海马神经递质调控的影响［J］.中成药，2020，42（10）：2751-2755.doi：10.3969/j.issn.1001-1528.2020.10.041http://dx.doi.org/10.3969/j.issn.1001-1528.2020.10.041.
陈建，曾智锐，雷珊，等.木犀草苷对MCF-7细胞增殖、迁移、侵袭的影响及其机制［J］.中成药，2022，44（2）：587-592.doi：10.3969/j.issn.1001-1528.2022.02.048http://dx.doi.org/10.3969/j.issn.1001-1528.2022.02.048.
吕蕊，徐文.金银花不同花期有机酸、木犀草苷、花青素与抗氧化活性关系［J］.分子植物育种，2021，19（22）：7579-7587.doi：10.13271/j.mpb.019.007579http://dx.doi.org/10.13271/j.mpb.019.007579.
Cao Z，Xing C，Cheng X，et al.Luteolin attenuates APEC-induced oxidative stress and inflammation via inhibiting the HMGB1/TLR4/NF-κB signal axis in the ileum of chicks［J］.Animals （Basel），2022，13（1）：83.doi：10.3390/ani13010083http://dx.doi.org/10.3390/ani13010083.
Li Y，Liang W，Guo C，et al.RenshenShouwu extract enhances neurogenesis and angiogenesis via inhibition of TLR4/NF-κB/NLRP3 signaling pathway following ischemic stroke in rats［J］.J Ethnopharmacol，2020，253：112616.doi：10.1016/j.jep.2020.112616http://dx.doi.org/10.1016/j.jep.2020.112616.
Song W，Wang T，Shi B，et al.Neuroprotective effects of microRNA-140-5p on ischemic stroke in mice via regulation of the TLR4/NF-κB axis［J］.Brain Res Bull，2021，168：8-16.doi：10.1016/j.brainresbull.2020.10.020http://dx.doi.org/10.1016/j.brainresbull.2020.10.020.
张赟，李珂，补王珍.电针调控Nrf2/HO-1通路对缺血缺氧性脑损伤大鼠小胶质细胞活化的影响［J］.天津医药，2023，51（2）：149-154.doi：10.11958/20220792http://dx.doi.org/10.11958/20220792.
王明鹤，杨峰，常成，等.木犀草素对缺氧缺血性脑损伤新生大鼠的神经保护作用［J］.中国病理生理杂志，2022，38（6）：993-1000.doi：10.3969/j.issn.1000-4718.2022.06.005http://dx.doi.org/10.3969/j.issn.1000-4718.2022.06.005.
李晓蕾，朱海生，麻瑞娟，等.基于TLR4/NF-κB通路探讨藏红花素对局灶性脑缺血再灌注损伤大鼠的神经保护作用［J］.康复学报，2022，32（6）：518-526.doi：10.3724/SP.J.1329.2022.06007http://dx.doi.org/10.3724/SP.J.1329.2022.06007.
Longa EZ，Weinstein PR，Carlson S，et al.Reversible middle cerebral artery occlusion without craniectomy in rats［J］.Stroke，1989，20（1）：84-91.doi：10.1161/01.str.20.1.84http://dx.doi.org/10.1161/01.str.20.1.84.
Yu S，Doycheva DM，Gamdzyk M，et al.Activation of MC1R with BMS-470539 attenuates neuroinflammation via cAMP/PKA/Nurr1 pathway after neonatal hypoxic-ischemic brain injury in rats［J］.J Neuroinflammation，2021，18（1）：26.doi：10.1186/s12974-021-02078-2http://dx.doi.org/10.1186/s12974-021-02078-2.
Turlova E，Wong R，Xu B，et al.TRPM7 mediates neuronal cell death upstream of calcium/calmodulin-dependent protein kinase Ⅱ and calcineurin mechanism in neonatal hypoxic-ischemic brain injury［J］.Transl Stroke Res，2021，12（1）：164-184.doi：10.1007/s12975-020-00810-3http://dx.doi.org/10.1007/s12975-020-00810-3.
Altamentova S，Rumajogee P，Hong J，et al.Methylprednisolone reduces persistent post-ischemic inflammation in a rat hypoxia-ischemia model of perinatal stroke［J］.Transl Stroke Res，2020，11（5）：1117-1136.doi：10.1007/s12975-020-00792-2http://dx.doi.org/10.1007/s12975-020-00792-2.
Xiang B，Geng R，Zhang Z，et al.Identification of the effect and mechanism of YiyiFuziBaijiang powder against colorectal cancer using network pharmacology and experimental validation［J］.Front Pharmacol，2022，13：929836.doi：10.3389/fphar.2022.929836http://dx.doi.org/10.3389/fphar.2022.929836.
Dong R，Huang R，Shi X，et al.Exploration of the mechanism of luteolin against ischemic stroke based on network pharmacology，molecular docking and experimental verification［J］.Bioengineered，2021，12（2）：12274-12293.doi：10.1080/21655979.2021.2006966http://dx.doi.org/10.1080/21655979.2021.2006966.
Sun C，Zhang Y，Liu M，et al.ShouhuiTongbian Capsules induce regression of inflammation to improve intestinal barrier in mice with constipation by targeted binding to Prkaa1：with no obvious toxicity［J］.Biomed Pharmacother，2023，161：114495.doi：10.1016/j.biopha.2023.114495http://dx.doi.org/10.1016/j.biopha.2023.114495.
Chen J，Yang C，Xu X，et al.The effect of focal cerebral ischemia-reperfusion injury on TLR4 and NF-κB signaling pathway［J］.Exp Ther Med，2018，15（1）：897-903.doi：10.3892/etm. 2017.5463http://dx.doi.org/10.3892/etm.2017.5463.
Chen X，Yao Z，Peng X，et al.Eupafolin alleviates cerebral ischemia/reperfusion injury in rats via blocking the TLR4/NF-κB signaling pathway［J］.Mol Med Rep，2020，22（6）：5135-5144.doi：10.3892/mmr.2020.11637http://dx.doi.org/10.3892/mmr.2020.11637.
肖杰，杨立基，赵琳娜，等.舒脑欣滴丸对脑缺血再灌注大鼠肠道炎症微环境及TLR4/NF-κB信号通路的影响［J］.中国中西医结合杂志，2023，43（1）：83-89.doi：10.7661/j.cjim.20220707.056http://dx.doi.org/10.7661/j.cjim.20220707.056.
Yang F，Li Y，Sheng X，et al.Paeoniflorin treatment regulates TLR4/NF-κB signaling，reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury［J］.Korean J Physiol Pharmacol，2021，25（2）：97-109.doi：10.4196/kjpp.2021. 25.2.97http://dx.doi.org/10.4196/kjpp.2021.25.2.97.
Wang Z，Chen W，Li Y，et al.Reduning injection and its effective constituent luteoloside protect against sepsis partly via inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways［J］.J Ethnopharmacol，2021，270：113783.doi：10.1016/j.jep.2021. 13783http://dx.doi.org/10.1016/j.jep.2021.13783.
0
Views
1
下载量
0
CSCD
- L-PDFDownload
- WORDDownload
- Meta-XMLDownload
- BibTeXDownload
- EndnoteDownload
- RefMan Download
- NoteExpressDownload
- NoteFirstDownload
Publicity Resources
Related Articles
Related Author
Related Institution
- Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19
京公网安备11010802024621 - It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
- Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.
