毛蕊异黄酮对脑出血后继发急性炎症损伤的改善作用及机制

柳晓蕊; 许智朝; 王兆涛; 张媚媚; 简晓顺; 彭怀东

doi:10.6039/j.issn.1001-0408.2023.16.04

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毛蕊异黄酮对脑出血后继发急性炎症损伤的改善作用及机制

药学研究 | 更新时间：2023-08-24

- 毛蕊异黄酮对脑出血后继发急性炎症损伤的改善作用及机制
- Improvement effect and mechanism of calycosin on acute inflammatory injury secondary to intracerebral hemorrhage
- 中国药房 2023年34卷第16期页码：1936-1942
- 作者机构：
  
  1.广州医科大学附属肿瘤医院药学部，广州　510095
  2.广州医科大学附属第二医院神经外科，广州　510260
  3.广州医科大学附属第二医院药学部，广州　510260
- 作者简介：
  
  主管药师，硕士。研究方向：小分子化合物抗炎、抗肿瘤。电话：020-66673666。E-mail：climbmm@163.com
  主管药师，硕士。研究方向：临床药学及小分子化合物抗炎、抗肿瘤。电话：020-34152376。E-mail：phdloveyou@163.com
- 基金信息：
  
  国家自然科学基金资助项目(81901117);广东省自然科学基金面上项目(2019A1515010926);广东省医学科学技术研究基金项目(A2022306);广州市卫生健康科技项目(20221A011098)
- DOI：10.6039/j.issn.1001-0408.2023.16.04
  中图分类号： R965
- 纸质出版日期：2023-08-30，
  
  收稿日期：2023-02-06，
  
  修回日期：2023-07-16，
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柳晓蕊,许智朝,王兆涛等.毛蕊异黄酮对脑出血后继发急性炎症损伤的改善作用及机制 ^Δ[J].中国药房,2023,34(16):1936-1942.

LIU Xiaorui,XU Zhichao,WANG Zhaotao,et al.Improvement effect and mechanism of calycosin on acute inflammatory injury secondary to intracerebral hemorrhage[J].ZHONGGUO YAOFANG,2023,34(16):1936-1942.
柳晓蕊,许智朝,王兆涛等.毛蕊异黄酮对脑出血后继发急性炎症损伤的改善作用及机制 ^Δ[J].中国药房,2023,34(16):1936-1942. DOI： 10.6039/j.issn.1001-0408.2023.16.04.

LIU Xiaorui,XU Zhichao,WANG Zhaotao,et al.Improvement effect and mechanism of calycosin on acute inflammatory injury secondary to intracerebral hemorrhage[J].ZHONGGUO YAOFANG,2023,34(16):1936-1942. DOI： 10.6039/j.issn.1001-0408.2023.16.04.

摘要

目的

探讨毛蕊异黄酮（CA）对脑出血后继发急性炎症损伤的改善作用及机制。

方法

以雄性C57BL/6小鼠为对象，通过基底节注射Ⅶ型胶原酶构建脑出血模型，分为假手术组（以磷酸盐缓冲液代替胶原酶）、模型组、不同剂量（15、30、60、120 mg/kg）CA组。在以改良神经功能缺损程度（mNSS）评分筛选干预剂量的基础上，检测各组小鼠的脑出血体积、脑含水量，脑组织中离子钙结合衔接分子1（Iba1）和脑组织中Toll样受体4（TLR4）及其下游炎症因子[肿瘤坏死因子α（TNF-α）、诱导型一氧化氮合酶（iNOS）、白细胞介素1β（IL-1β）]的表达情况，以及脑组织中细胞的凋亡情况。体外培养原代小胶质细胞，检测其中TLR4及其下游炎症因子的表达情况；体外共培养原代神经元与原代小胶质细胞，检测其中神经元的凋亡情况。

结果

选取30、60 mg/kg作为CA的干预剂量进行后续实验。与假手术组比较，模型组小鼠出现了脑出血现象，脑出血体积和脑含水量均显著升高（

＜0.05），脑组织中Iba1蛋白的表达阳性率显著升高，脑组织中TLR4、TNF-α、IL-1β、iNOS蛋白的相对表达水平均显著上调，细胞凋亡率亦显著增加（

＜0.05）；与模型组比较，30、60 mg/kg CA组小鼠上述指标均显著改善（

＜0.05）。CA显著降低了原代小胶质细胞中TLR4及其下游炎症因子的相对表达水平，显著减少了原代神经元与原代小胶质细胞共培养体系中神经元的凋亡（

＜0.05）。

结论

CA可发挥脑保护作用，可能与抑制TLR4介导的炎症反应而减轻脑出血后继发的急性炎症损伤有关。

Abstract

OBJECTIVE

To investigate the improvement effect and mechanism of calycosin （CA） on acute inflammatory injury secondary to intracerebral hemorrhage.

METHODS

Male C57BL/6 mice were injected with type Ⅶ collagenase into the basal ganglia to establish an intracerebral hemorrhage model， which were divided into sham-operation group（phosphate buffered saline instead of collagenase）， model group， and different CA dose groups（15，30，60，120 mg/kg）. Based on the modified neurological severity score （mNSS） to screen the intervention doses， the volume of intracerebral hemorrhage， brain water content， the expressions of ionized calcium-binding adaptor molecule 1 （Iba1） in brain tissue， Toll-like receptor 4 （TLR4） and its downstream inflammatory factors [tumor necrosis factor-α （TNF-α）， inducible nitric-oxide synthase （iNOS）， interleukin-1β （IL-1β）] in brai

n tissue， and the apoptosis of cells in brain tissue were detected. Primary microglia were cultured

in vitro

， and the expressions of TLR4 and its downstream inflammatory factors were detected. Primary neurons and primary microglia were co-cultured

in vitro

， and the apoptosis of neurons was detected.

RESULTS

The doses of 30 mg/kg and 60 mg/kg were selected as intervention doses of CA for subsequent experiments. Compared with the sham-operation group， the mice in the model group had cerebral hemorrhage， the volume of cerebral hemorrhage and brain water content were significantly increased （

＜0.05）； the positive expression rate of Iba1 protein in brain tissue was significantly increased， and the relative expression levels of TLR4， TNF-α， IL-1β and iNOS protein in brain tissue were up-regulated significantly. The apoptosis rate also increased significantly （

＜0.05）. Compared with model group， the above indexes of the mice in the 30 and 60 mg/kg CA groups were significantly improved （

＜0.05）. CA significantly reduced the relative expression levels of TLR4 and its downstream inflammatory factors in microglia， and reduced the apoptosis of neurons in the co-culture system of primary neurons and primary microglia （

＜0.05）.

CONCLUSIONS

CA can exert a protective effect on the brain， which may be related to relieving the secondary acute inflammatory injury after intracerebral hemorrhage by inhibiting TLR4-mediated inflammatory response.

关键词

毛蕊异黄酮脑出血继发急性炎症损伤Toll样受体4小胶质细胞

Keywords

intracerebral hemorrhagesecondary acute inflammatory injuryToll-like receptor 4microglia

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