三七总皂苷抑制小鼠星形胶质细胞活化缓解完全弗氏佐剂所致炎性痛

doi:10.16098/j.issn.0529-1356.2024.01.004

解剖学报 ›› 2024, Vol. 55 ›› Issue (1): 25-31.doi: 10.16098/j.issn.0529-1356.2024.01.004

三七总皂苷抑制小鼠星形胶质细胞活化缓解完全弗氏佐剂所致炎性痛

袁蕾¹ 杨智伟¹ 杨惠² 刘政海³ 何洁⁴ 万炜^1*

1.海南省热带脑科学研究与转化重点实验室，海口 571199; 2.赣州市人民医院病理科，江西赣州 341000; 3.南华大学衡阳医学院应用解剖学与生殖医学研究所，湖南衡阳 421001; 4.海南医学院病理学教研室，海口 571199

收稿日期:2023-07-06 修回日期:2023-09-01 出版日期:2024-02-06 发布日期:2024-02-06
通讯作者: 万炜 E-mail:david-wan@163.com
基金资助:
热量限制在辐射小鼠认知障碍中的机制研究;VDAC1通过调节神经发生在电离辐射致小鼠认知障碍中的作用

Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice

YUAN Lei¹ YANG Zhi-wei¹ YANG Hui² LIU Zheng-hai³ HE Jie⁴ WAN Wei^1*

1.Key Laboratory of Brain Science Research & Transformation in Tropical Environment of Hainan Province, Haikou 571199,China；
2.Department of Pathology, Ganzhou People’s Hospital, Jiangxi Ganzhou 341000,China； 3.Clinical Anatomy and Reproductive Medicine Application Institute，School of Medicine，University of South China，Hu’nan Hengyang 421001,China； 4.Department of Pathology，Hainan Medical University, Haikou 571199,China

Received:2023-07-06 Revised:2023-09-01 Online:2024-02-06 Published:2024-02-06
Contact: WAN Wei E-mail:david-wan@163.com

摘要/Abstract

摘要：

目的探讨三七总皂苷（PNS）对完全弗氏佐剂（CFA）所致慢性炎性疼痛小鼠模型的镇痛作用及可能机制。方法 48只C57BL/6J雄性小鼠随机分成生理盐水对照组（Ctrl）、CFA组（CFA）、CFA+ PNS组、CFA +地塞米松（DEX）组（CFA+DEX）。采用Von Frey纤维丝检测小鼠机械疼痛；采用免疫组织化学法检测脊髓后角胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞数目和形态结构变化；采用Western blotting 检测各组小鼠相应节段脊髓GFAP、核苷酸结合寡聚化结构域（NOD）样受体热蛋白结构域相关蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）、Caspase-1、白细胞介素（IL）-1β和IL-18的表达。结果与Ctrl组相比，CFA组小鼠机械痛阈值在第1、3、5、7、14天明显下降，小鼠脊髓NLRP3、ASC、Caspase-1、IL-1β和IL-18的表达均显著增加。PNS干预可缓解模型小鼠机械痛觉，下调小鼠脊髓NLRP3、ASC、Caspase-1、IL-1β和IL-18的表达，且与CFA+DEX组表达差异无显著性。免疫组织化学结果显示，与Ctrl组相比，CFA组小鼠脊髓后角GFAP阳性细胞数目显著增多；PNS干预后CFA+ PNS组小鼠脊髓后角 GFAP阳性细胞数目减少；DEX干预后对小鼠脊髓后角GFAP阳性细胞数目没有明显影响。Western blotting 结果显示，与Ctrl组相比，CFA组小鼠脊髓GFAP表达明显增加；PNS干预后CFA+ PNS组小鼠脊髓GFAP表达明显减少，DEX干预后对小鼠脊髓后角GFAP表达没有明显影响。结论 PNS对炎性痛具有较好的缓解作用，其机制可能与抑制星形胶质细胞活化以及减少NLRP3炎性小体激活有关。

关键词: 三七总皂苷, 星形胶质细胞, 炎性痛, 核苷酸结合寡聚化结构域样受体热蛋白结构域相关蛋白3, 免疫组织化学, 免疫印迹法, 小鼠

Abstract:

Objective To analyse the analgesic effect and possible mechanism of panax notoginseng saponin (PNS) on mouse models of chronic inflammatory pain caused by complete Freund’s adjuvant (CFA). Methods A total of 48 male C57BL/6J mice were divided randomly into four groups: normal saline control group (Ctrl), CFA group (CFA), CFA + PNS group (CFA+PNS), CFA + dexamethasone (DEX) group (CFA+DEX). Von Frey filaments were used to detect mechanical pain in mice. Immunohistochemistry was used to detect the number and morphological changes of glial fibrillary acidic protein (GFAP) positive astrocytes. Western blotting was used to detect the expressions of GFAP, nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in mice’s spinal cord segments in each group. Results Compared with the Ctrl group, mice in the CFA group showed a significant decrease in mechanical pain thresholds at day 1, day 3, day 5, day 7, and day 14. Additionally, there was a significant decrease in NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of the mice. PNS intervention could relieve mechanical pain and down-regulate the expressions of NLRP3, ASC, Caspase-1, IL-1β and IL-18 in the spinal cord of mice, with no significant difference compared with the CFA+DEX group. CFA group mice had significantly more GFAP positive cells in their posterior horns than Ctrl group mice, as measured by immunohistochemistry; PNS intervention decreased the number of GFAP positive cells in the posterior horn of the spinal cord in model mice；DEX had no effect on the number of GFAP positive cells in the dorsal horn of spinal cord. According to Western blotting results, GFAP expression in the spinal cord of the CFA group was significantly more than that of the Ctrl group; PNS intervention significantly reduced GFAP expression in the spinal cord of CFA group mice；DEX had no effect on the expression of GFAP in the posterior horn of spinal cord. Conclusion PNS has a good alleviating effect on inflammatory pain, and its mechanism may be related to inhibition of astrocyte activation and NLRP3 inflammasome activation.

Key words:

Panax notoginseng saponins, Astrocyte, Inflammatory pain, Nucleotide-binding and oligomerization domain-like receptor thermal protein domain associated protein 3, Immunohistochemistry, Western blotting, Mouse

中图分类号:

R322.81

袁蕾杨智伟杨惠刘政海何洁万炜.

三七总皂苷抑制小鼠星形胶质细胞活化缓解完全弗氏佐剂所致炎性痛 [J]. 解剖学报, 2024, 55(1): 25-31.

YUAN Lei YANG Zhi-wei YANG Hui LIU Zheng-hai HE Jie WAN Wei.

Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice [J]. Acta Anatomica Sinica, 2024, 55(1): 25-31.

参考文献

[1] Li J, Chen Y, Liu J, et al. Elevated expression and activity of sodium leak channel contributes to neuronal sensitization of inflammatory pain in rats ［J］. Front Mol Neurosci,2021,14:723395.

［2］Gu Y, Chen S, Mo Y, et al. Electroacupuncture attenuates CFA-induced inflammatory pain by regulating CaMKⅡ［J］. Neural Plast,2020,2020:8861994.

［3］Li J, Su S, Xu Z, et al. Potential roles of gut microbiota and microbial metabolites in chronic inflammatory pain and the mechanisms of therapy drugs［J］. Ther Adv Chronic Dis,2022,13:20406223221091177.

［4］Tang J, Bair M, Descalzi G. Reactive astrocytes: critical players in the development of chronic pain［J］. Front Psychiatry, 2021,12:682056.

［5］Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch［J］. Nat Rev Neurosci, 2019,20(11):667-685.

［6］Gorina YV, Salmina AB, Erofeev AI, et al. Astrocyte activation markers［J］. Biochemistry (Mosc), 2022,87(9):851-870.

［7］De la Luz-Cuellar YE, Rodríguez-Palma EJ, Franco-Enzástiga ú, et al. Blockade of spinal α5-GABAA receptors differentially reduces reserpine-induced fibromyalgia-type pain in female rats［J］. Eur J Pharmacol,2019,858:172443.

［8］Zhang H, Li F, Li WW, et al. The inflammasome as a target for pain therapy［J］. Br J Anaesth, 2016,117(6):693-707.

［9］O’Brien WT, Pham L, Symons GF, et al. The NLRP3 inflammasome in traumatic brain injury: potential as a biomarker and therapeutic target［J］. J Neuroinflammation,2020,17(1):104.

［10］Huang YD, Cheng JX, Shi Y, et al. Panax notoginseng: a review on chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology in recent five years［J］. China Journal of Chinese Materia Medica,2022,47(10):2584-2596.（in Chinese）

黄依丹,成嘉欣,石颖，等.近五年三七化学成分、色谱分析、三七提取物和药理活性的研究进展［J］.中国中药杂志,2022,47(10):2584-2596.

［11］Fan YH, Xu Ch, Fei YR, et al. Determination of contents and encapsulation efficiencies of five saponins in Panax notoginseng saponins transfersomes［J］. Chinese Traditional and Herbal Drugs,2022,53(10):3006-3013. （in Chinese）

范煜航,徐畅,费雅蓉,等.三七总皂苷传递体中5种皂苷类成分含量与包封率的测定研究［J］.中草药,2022,53(10):3006-3013.

［12］Uzayisenga R, Ayeka PA, Wang Y. Anti-diabetic potential of Panax notoginseng saponins (PNS): a review［J］. Phytother Res,2014,28(4):510-516.

［13］Ma CH, Chou WC, Wu CH, et al. Ginsenoside Rg3 attenuates TNF-α-induced damage in chondrocytes through regulating SIRT1-mediated anti-apoptotic and anti-inflammatory mechanisms［J］. Antioxidants (Basel), 2021,10(12):1972.

［14］Shoaib RM, Ahsan MZ, Akhtar U, et al. Ginsenoside Rb1, a principal effective ingredient of Panax notoginseng, produces pain antihypersensitivity by spinal microglial dynorphin A expression［J］. Neurosci Res, 2023, 188:75-87.

［15］Chaplan SR, Bach FW, Pogrel JW, et al. Quantitative assessment of tactile allodynia in the rat paw［J］. J Neurosci Methods, 1994,53(1):55-63.

［16］Li DY, Gao SJ, Sun J, et al. Targeting the nitric oxide/cGMP signaling pathway to treat chronic pain［J］. Neural Regen Res, 2023,18(5):996-1003.

［17］Deng D, Xu F, Ma L, et al. Electroacupuncture alleviates CFA-induced inflammatory pain via PD-L1/PD-1-SHP-1 pathway［J］. Mol Neurobiol, 2023,60(5):2922-2936.

［18］Ning N, Dang X, Bai C, et al. Panax notoginsenoside produces neuroprotective effects in rat model of acute spinal cord ischemia-reperfusion injury［J］. J Ethnopharmacol, 2012,139(2):504-512.

［19］Zhang RL，Wan W，Liu H，et al. Panax notoginseng saponins pretreatment affects the inflammatory visceral pain via upregulation of the glutamine synthetase in the rat spinal dorsal horn［J］. Acta Anatomica Sinica, 2015,24(1):20-24.（in Chinese）

张仁丽,万炜,刘红,等.三七总皂苷预处理对炎性内脏痛大鼠脊髓背角谷氨酰胺合成酶表达的影响［J］.解剖学报,2015,46(1):20-24.

［20］Khafagy HF, Refaat AI, El-Sabae HH, et al. Efficacy of epidural dexamethasone versus fentanyl on postoperative analgesia［J］. J Anesth, 2010,24(4):531-536.

［21］Liu Y, Latremoliere A, Li X, et al. Touch and tactile neuropathic pain sensitivity are set by corticospinal projections［J］. Nature, 2018,561(7724):547-550.

［22］Ducza L, Szücs P, Hegedüs K, et al. NLRP2 is overexpressed in spinal astrocytes at the peak of mechanical pain sensitivity during complete freund adjuvant-induced persistent pain［J］. Int J Mol Sci, 2021, 22(21):11408.

［23］Xu H, Chen J, Chen P, et al. Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases［J］. Acta Pharm Sin B, 2023, 13(2):678-693.

［24］Lin J, Ren J, Zhu B, et al. Dimethyl itaconate attenuates CFA-induced inflammatory pain via the NLRP3/ IL-1β signaling pathway［J］. Front Pharmacol, 2022, 13:938979.

［25］de Graaf L, Aarts F. Dexamethason［J］. Nursing (Maarssen)，2020, 26(12):52-55.

[1]	陈培陈小菊杜竺蔓汪操会 . 贝母素甲改善脂多糖联合烟雾诱导小鼠慢性阻塞性肺疾病的机制[J]. 解剖学报, 2024, 55(2): 215-221.
[2]	吴跃武胡斌过小冬付琴邹志佳 . 微小RNA-30a调控丝裂原活化蛋白激酶通路对主动脉夹层大鼠的影响[J]. 解剖学报, 2024, 55(2): 222-228.
[3]	杨珊珊潘宇翔郑婉王政 . Exendin-4抑制亲环蛋白A减轻动脉粥样硬化模型小鼠病理表型[J]. 解剖学报, 2024, 55(2): 229-236.
[4]	程全成丁慧如王子元方金玉张晓丽张卫光. 水通道蛋白9商品化抗体和自制抗体识别位点的分析和应用[J]. 解剖学报, 2024, 55(2): 237-240.
[5]	汪洋吴振华吕红博罗洞波 . 上皮细胞转化序列2通过调控p33生长抑制因子1表达影响食管鳞状细胞癌细胞的体外转移活性[J]. 解剖学报, 2024, 55(2): 203-209.
[6]	任健陈晓燕. 慢病毒载体介导的类固醇生成因子-1沉默调控子宫内膜基质细胞蜕膜化与自噬[J]. 解剖学报, 2024, 55(2): 188-195.
[7]	段兆达杨力陈浩伦刘腾腾郑立扬徐冬垚吴春云. 灯盏乙素通过环状GMP-AMP合酶-干扰素基因刺激因子通路抑制BV-2小胶质细胞介导的神经炎症[J]. 解剖学报, 2024, 55(2): 133-142.
[8]	周泽宇马蕴涵李佳瑞胡余梦袁博张银娟于晓敏付秀美. 脱细胞异体神经移植物联合电针对坐骨神经损伤大鼠脊神经节的保护作用及机制[J]. 解剖学报, 2024, 55(2): 143-149.
[9]	李允争孙秋颖唐中生朱世杰 . 穴位埋线对血管性痴呆大鼠学习记忆功能及海马微血管新生的影响[J]. 解剖学报, 2024, 55(2): 150-157.
[10]	金思璇于宁孙丰润马超. 远端脊髓节段星形胶质细胞活化介导神经损伤诱发的播散性疼痛[J]. 解剖学报, 2024, 55(2): 167-173.
[11]	洪晓敏李三强崔钦奕郑润月杨孟利罗仁利李前辉 . 酒精性肝纤维化核因子κB信号通路与性别的差异 [J]. 解剖学报, 2024, 55(1): 55-61.
[12]	魏茜茜李超红赵晨露唐家萍刘玉珍. 大鼠颈上神经节中Ⅰ组代谢型谷氨酸受体表达及慢性间歇性低氧对其的影响 [J]. 解剖学报, 2024, 55(1): 3-9.
[13]	马婷婷陈建红刘爱翠李海宁. 抑制lncRNA TUG1下调核苷酸结合寡聚结构域样受体蛋白1炎症小体在延缓阿尔茨海默病进展的作用 [J]. 解剖学报, 2024, 55(1): 32-42.
[14]	邹成功冯浩陈兵唐辉邵川孙谋杨荣何家全. 创伤性颅脑损伤中神经功能障碍与认知功能损伤的动态变化 [J]. 解剖学报, 2024, 55(1): 43-48.
[15]	吕海燕沈西雅赵富生朱梅. 松茸多糖对 1-甲基-4-苯基-吡啶离子诱导 PC12 细胞损伤的影响 [J]. 解剖学报, 2024, 55(1): 49-54.

三七总皂苷抑制小鼠星形胶质细胞活化缓解完全弗氏佐剂所致炎性痛

Panax notoginseng saponin relieving the inflammatory pain caused by complete Freund’s adjuvant by inhibiting the activation of astrocytes in mice

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价