Intervention Effect of Ruyi Zhenbao Pills on Mice with Central Pain After Thalamic Stroke

Kexin JIA; Gejia ZHONG; Chunyan ZHU; Luochangting FANG; Xiaoxiao WANG; Tengteng XU; Zhixing HU; Cairen JUEJIA; Xianda HU; Chunfang LIU; Na LIN

doi:10.13422/j.cnki.syfjx.20221539

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Intervention Effect of Ruyi Zhenbao Pills on Mice with Central Pain After Thalamic Stroke

更新时间：2022-07-14

- Intervention Effect of Ruyi Zhenbao Pills on Mice with Central Pain After Thalamic Stroke
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 16, Pages: 82-89(2022)
- 作者机构：
  
  1.中国中医科学院中药研究所，北京 100700
  2.中国藏学研究中心北京藏医院，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20221539
  CLC： R2-0;R33;R289;R743.34
- Received：12 April 2022，
  
  Published Online：10 June 2022，
  
  Published：20 August 2022
- 稿件说明：
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贾可欣,仲格嘉,朱春燕等.如意珍宝丸对小鼠丘脑出血后中枢痛的干预作用[J].中国实验方剂学杂志,2022,28(16):82-89.

JIA Kexin,ZHONG Gejia,ZHU Chunyan,et al.Intervention Effect of Ruyi Zhenbao Pills on Mice with Central Pain After Thalamic Stroke[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(16):82-89.
贾可欣,仲格嘉,朱春燕等.如意珍宝丸对小鼠丘脑出血后中枢痛的干预作用[J].中国实验方剂学杂志,2022,28(16):82-89. DOI： 10.13422/j.cnki.syfjx.20221539.

JIA Kexin,ZHONG Gejia,ZHU Chunyan,et al.Intervention Effect of Ruyi Zhenbao Pills on Mice with Central Pain After Thalamic Stroke[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(16):82-89. DOI： 10.13422/j.cnki.syfjx.20221539.

摘要

目的

观察如意珍宝丸（RYZBW）对小鼠丘脑卒中后中枢痛的干预作用，并初步探索其作用机制。

方法

利用Ⅳ型胶原酶立体定位注射小鼠下丘脑诱导小鼠卒中后中枢疼痛（CPSP）模型，将小鼠分为假手术组、模型组、RYZBW低、中、高（0.65、1.3、2.6 g·kg

-1

）剂量组和阳性药普瑞巴林组（0.075 g·kg

-1

）。给药组造模小鼠术后7 d开始按照体质量每天1次灌胃给药，共给药25 d，假手术组及模型组小鼠给予等体积生理盐水；期间检测不同时间点的机械痛敏、冷痛敏，原位末端标记法（TUNEL）检测脑组织细胞凋亡状态，液相悬浮芯片技术对36种经典广谱炎症因子进行定量分析，筛选差异分子，并采用蛋白免疫印迹法（Western blot）和酶联免疫吸附测定法（ELISA）对其验证。

结果

与假手术组比较，模型组机械痛阈值、冷敏痛阈值显著改变（

0.01），TUNEL结果反映脑细胞凋亡明显，Western blot和ELISA结果显示下丘脑组织和血清中白细胞介素-1

（IL-1

）和趋化因子配体5（CCL5）表达增加，而促血管生成素-2（Ang-2）、粒细胞-集落刺激因子（G-CSF）和IL-4的表达均显著降低（

0.01）；与模型组比较，RYZBW各剂量组可显著升高脑卒中后小鼠的机械痛阈值，降低冷敏痛阈值，降低下丘脑细胞凋亡比例（

0.01），下丘脑组织和/血清中IL-1

和CCL5表达降低，而Ang-2、G-CSF、IL-4的表达均明显升高（

0.05）。

结论

RYZBW可缓解CPSP小鼠的痛觉过敏，其机制与调节促炎/抗炎因子IL-1α、CCL5、IL-4、G-CSF和Ang-2的表达有关。

Abstract

Objective

To observe the intervention effect of Ruyi Zhenbao pills （RYZBP） on central pain after thalamic stroke in mice and explore the underlying mechanism.

Method

The central post-stroke pain syndrome （CPSP） model was induced by stereotactic injection of type Ⅳ collagenase into the hypothalamus in mice. The mice were divided into a sham group， a model group， low-， medium-， and high-dose RYZBP groups （0.65， 1.3， 2.6 g·kg

-1

）， and a pregabalin group （0.075 g·kg

-1

）. Seven days after modeling， the mice in the groups with drug intervention were administered with corresponding drugs by gavage according to the body mass， once per day for 25 days， while those in the sham group and the model group received an equal volume of normal saline. During this period， mechanical pain and cold pain were detected at different time points， and the apoptotic state of brain tissue cells was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. The 36 classical broad-spectrum inflammatory factors were quantitatively analyzed by liquid-phase chip technology， and differential molecules were screened out and verified by Western blot and enzyme-linked immunosorbent assay （ELISA）.

Result

Compared with sham operation group

mechanical pain threshold and cold sensitive pain threshold in model group were significantly changed （

0.01）. TUNEL results showed that apoptosis of brain cells was obvious. Western blot and ELISA results showed that the expressions of interleukin-1

(IL-1

) and chemokine ligand 5 (CCL5) increased in hypothalamus tissue and serum， while the expressions of Ang-2

granulocyte-colony-stimulating factor (G-CSF) and IL-4 decreased significantly （

0.01）. Compared with model group， RYZBW dose groups significantly increased mechanical pain threshold， decreased cold sensitivity pain threshold， decreased hypothalamus cell apoptosis ratio （

0.01）， decreased the expression of IL-1

and CCL5 in hypothalamus tissue and serum， while the expression of ANG-2， G-CSF and IL-4 were significantly increased （

0.05）.

Conclusion

RYZBP can relieve hyperalgesia in CPSP mice， and its mechanism is related to the regulation of the expression of pro-/anti-inflammatory factors IL-1

， CCL5， IL-4， G-CSF， and Ang-2.

关键词

Keywords

references

BOWSHER D . Central pain：Clinical and physiological characteristics ［J］. J Neurol Neurosurg Psychiatry ， 1996 ， 61 （ 1 ）： 62 - 69 .

AKYUZ G ， KURU P . Systematic review of central post stroke pain：What is happening in the central nervous system？［J］. Am J Phys Med Rehabil ， 2016 ， 95 （ 8 ）： 618 - 627 .

CHEN C C ， CHUANG Y F ， HUANG A C ， et al . The antalgic effects of non-invasive physical modalities on central post-stroke pain：A systematic review ［J］. J Phys Ther Sci ， 2016 ， 28 （ 4 ）： 1368 - 1373 .

许宗仁，包旭宏，田其健 . 如意珍宝丸（片）的研究综述［J］. 中国民间疗法， 2020 ， 28 （ 13 ）： 106 - 109 .

王海苹 . 藏药如意珍宝丸临床应用现状［J］. 中国民族医药杂志， 2014 ， 20 （ 1 ）： 46 - 49 .

罗亚敏，任小巧，宋慧荣，等 . 藏药如意珍宝丸20年研究进展［J］. 中国民族医药杂志， 2017 ， 23 （ 7 ）： 69 - 72 .

谭敬，肖新莉，陈新林，等 . 采用Ⅳ型胶原酶建立小鼠脑出血模型［J］. 陕西医学杂志， 2014 ， 43 （ 5 ）： 522 - 525 .

李佳豪，田聪敏，池宏宇，等 . 瘀血痹片通过抑制外周炎症缓解慢性炎性痛小鼠痛觉过敏及足肿胀［J］. 中国实验方剂学杂志， 2021 ， 27 （ 10 ）： 31 - 37 .

金宇林，徐海平，宋兴荣，等 . 大鼠神经病理性痛时脊髓kindlin-1/Wnt3a信号通路与炎症反应的关系［J］. 中华麻醉学杂志， 2021 ， 41 （ 3 ）： 319 - 322 .

王新颖，任安，李梦绮，等 . TLRs/IRAK1/TRAF6/NF- κ B信号通路介导神经炎症参与神经病理性痛的研究进展［J］. 赣南医学院学报， 2020 ， 40 （ 9 ）： 917 - 923 .

MIKA J ， KOROSTYNSKI M ， KAMINSKA D ， et al . Interleukin-1 alpha has antiallodynic and antihyperalgesic activities in a rat neuropathic pain model ［J］. Pain ， 2008 ， 138 （ 3 ）： 587 - 597 .

MA F ， ZHANG L ， OZ H S ， et al . Dysregulated TNF- α promotes cytokine proteome profile increases and bilateral orofacial hypersensitivity ［J］. Neuroscience ， 2015 ， 300 ： 493 - 507

ShamASH S ， REICHERT F ， ROTSHENKER S . The cytokine network of Wallerian degeneration：Tumor necrosis factor-alpha，interleukin-1alpha，and interleukin-1beta ［J］. J Neurosci ， 2002 ， 22 （ 8 ）： 3052 - 3060 .

BOBINSKI F ， TEIXEIRA J M ， SLUKA K A ， et al . Interleukin-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain ［J］. Pain ， 2018 ， 159 （ 3 ）： 437 - 450 .

KIGUCHI N ， KOBAYASHI Y ， SAIKA F ， et al . Peripheral interleukin-4 ameliorates inflammatory macrophage-dependent neuropathic pain ［J］. Pain ， 2015 ， 156 （ 4 ）： 684 - 693 .

KHORASANIZADEH M ， ESKIAN M ， VACCARO A R ， et al . Granulocyte colony-stimulating factor （G-CSF） for the treatment of spinal cord injury ［J］. CNS Drugs ， 2017 ， 31 （ 11 ）： 911 - 937 .

ZHANG E ， LEE S ， YI M H ， et al . Expression of granulocyte colony-stimulating factor 3 receptor in the spinal dorsal horn following spinal nerve ligation-induced neuropathic pain ［J］. Mol Med Rep ， 2017 ， 16 （ 2 ）： 2009 - 2015 .

SHIUE S J ， RAU R H ， SHIUE H S ， et al . Mesenchymal stem cell exosomes as a cell-free therapy for nerve injury-induced pain in rats ［J］. Pain ， 2019 ， 160 （ 1 ）： 210 - 223 .

刘发生，李帅，郭立峰，等 . HMGB-1、cTnI及Ang2与急诊多发伤血管损伤、院内死亡风险的关系［J］. 分子诊断与治疗杂志， 2021 ， 13 （ 8 ）： 1349 - 1352 .

ZHOU H J ， QIN L ， ZHANG H ， et al . Endothelial exocytosis of angiopoietin-2 resulting from CCM3 deficiency contributes to cerebral cavernous malformation ［J］. Nat Med ， 2016 ， 22 （ 9 ）： 1033 - 1042 .

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