Effects of Tiaoxin Bushen Formula on microglial activation and neuroinflammatory responses in prefrontal cortex of mice with Alzheimer’s disease

Yining GU; Zhiyuan LU; Zongtao BA; Chenyi ZHAO; Guang YANG; Yuting TONG; Ahelijiang REAILA; Xingyu WANG; Jian WANG; Ying XU

doi:10.16305/j.1007-1334.2022.2201086

您当前的位置：

首页 >

文章列表页 >

Effects of Tiaoxin Bushen Formula on microglial activation and neuroinflammatory responses in prefrontal cortex of mice with Alzheimer’s disease

更新时间：2022-08-12

- Effects of Tiaoxin Bushen Formula on microglial activation and neuroinflammatory responses in prefrontal cortex of mice with Alzheimer’s disease
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 8, Pages: 84-89(2022)
- 作者机构：
  
  1.上海中医药大学康复医学院（上海 201203）
  2.上海中医药大学基础医学院（上海 201203）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2201086
  CLC：
扫描看全文
顾祎宁,卢志园,巴宗韬等.调心补肾方对阿尔茨海默病小鼠前额皮质中小胶质细胞激活和神经炎症反应的影响[J].上海中医药杂志,2022,56(08):84-89.

GU Yining,LU Zhiyuan,BA Zongtao,et al.Effects of Tiaoxin Bushen Formula on microglial activation and neuroinflammatory responses in prefrontal cortex of mice with Alzheimer’s disease[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(08):84-89.
顾祎宁,卢志园,巴宗韬等.调心补肾方对阿尔茨海默病小鼠前额皮质中小胶质细胞激活和神经炎症反应的影响[J].上海中医药杂志,2022,56(08):84-89. DOI： 10.16305/j.1007-1334.2022.2201086.

GU Yining,LU Zhiyuan,BA Zongtao,et al.Effects of Tiaoxin Bushen Formula on microglial activation and neuroinflammatory responses in prefrontal cortex of mice with Alzheimer’s disease[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(08):84-89. DOI： 10.16305/j.1007-1334.2022.2201086.

摘要

目的,2,探讨调心补肾方（TXBSF）对早老素1/2条件性双基因敲除（PS cDKO）的阿尔茨海默病（AD）小鼠前额皮质中小胶质细胞激活和神经炎症反应的影响。,方法,2,选取60只3~3.5月龄的PS cDKO小鼠及其同窝野生型对照小鼠，分为野生型（WT）组、模型（PS cDKO）组和模型+TXBSF（PS cDKO+TXBSF）组，每组20只。野生型组和模型组小鼠均食用普通饲料，模型+TXBSF组小鼠给予含有TXBSF（17.918 g/kg）饲料喂养90 d，药物治疗结束后取材进行分子生物学检测。采用免疫组化染色法观察TXBSF对各组小鼠前额皮质中小胶质细胞的激活情况；qRT-PCR法检测TXBSF对各组小鼠前额皮质中促炎症因子环氧化酶-2（,COX,-,2,）、诱导性一氧化氮合酶（,iNOS,）、肿瘤坏死因子-α（,TNF,-,α,）、白介素-1β（,IL,-,1β,）和白介素-6（,IL,-,6,）mRNA水平的影响；Western blot法检测TXBSF对各组小鼠前额皮质中COX-2和iNOS蛋白表达的影响；ELISA法检测TXBSF对各组小鼠前额皮质中TNF-α、IL-6和IL-1β含量的影响。,结果,2,免疫组化染色结果显示，与模型小鼠相比，模型+TXBSF组小鼠表现出下降的阿米巴样小胶质细胞比例（,P,<,0.05）、较多的分支数（,P,<,0.05）、较长的平均长度（,P,<,0.05）以及较长的最长分支长度（,P,<,0.05）。qRT-PCR结果显示，与模型组小鼠相比，模型+TXBSF组小鼠,COX-2,、,iNOS,、,TNF-α,、,IL-1β,和,IL-6, mRNA表达下降（,P,<,0.05）。Western blot结果显示，与模型组小鼠相比，模型+TXBSF组小鼠前额皮质中COX-2和iNOS的蛋白表达水平显著降低（,P,<,0.05）。ELISA结果显示，与模型组小鼠相比，模型+TXBSF组小鼠前额皮质中TNF-α、IL-6和IL-1β水平显著下降（,P,<,0.05）。,结论,2,TXBSF可能通过抑制前额皮质中小胶质细胞的激活和神经炎症反应来改善AD小鼠的记忆障碍。

Abstract

Objective,2,To observe the effects of Tiaoxin Bushen Formula （TXBSF） on the activation of microglia and neuroinflammatory response in prefrontal cortex （PFC） of presenilin 1/2 conditional double knockout （PS cDKO） mice with Alzheimer’s disease.,Methods,2,Totally 60 PS cDKO mice aged 3-3.5 months and their littermates were randomly divided into three groups with 20 in each： wild type group （WT）， model group （PS cDKO） and model+TXBSF group （PS cDKO+TXBSF）. The mice in the WT and PS cDKO group were fed with standard chow， and the mice in the PS cDKO+TXBSF group were fed with standard chow containing TXBSF （17.918 g/kg） for 90 days. After drug administration， the mice were sacrificed for molecular biology detection. Immunohistochemical staining was used to observe the effect of TXBSF on the activation of microglia in PFC of mice in each group. qRT-PCR was used to analyze the effect of TXBSF on mRNA levels of proinflammatory factors in PFC of mice， such as cyclooxygenase-2 （,COX,-,2,）， inducible nitric oxide synthase （,iNOS,）， tumor necrosis factor-,α, （,TNF,-,α,）， interleukin-1β （,IL,-,1β,） and interleukin-6 （,IL,-,6,）. Western blot was used to detect the effect of TXBSF on the expressions of COX-2 protein and iNOS protein in PFC of mice in each group， and changes in the levels of TNF-α， IL-6 and IL-1β in PFC of mice in each group were measured by ELISA.,Results,2,Immunohistochemical staining showed that compared with PS cDKO mice， the mice with TXBSF demonstrated lower ratios of amoeboid microglia（,P<,0.05）， more branching numbers （,P<,0.05）， longer average branch length （,P<,0.05） and longer maximum branch length（,P<,0.05）. The result of qRT-PCR showed that TXBSF significantly inhibited ,COX,-,2,， ,iNOS,， ,TNF,-,α,，,IL,-,1β, and ,IL,-,6, mRNA expression levels（,P,<,0.05）. Western blot analysis showed that the protein expression levels of COX-2 and iNOS in PFC of PS cDKO mice treated with TXBSF were significantly lower than those in PS cDKO group （,P,<,0.05）. The result of ELISA showed that compared with those of PS cDKO mice， the treatment of TXBSF could significantly reduce the levels of TNF-α，IL-6 and IL-1β in PFC of PS cDKO mice （,P,<,0.05）.,Conclusion,2,TXBSF may improve the memory impairment by inhibiting the activation of microglia and neuroinflammatory responses in PFC of mice with Alzheimer’s disease.

关键词

阿尔茨海默病调心补肾方小胶质细胞神经炎症PS cDKO模型小鼠中药研究

Keywords

Alzheimer’s diseaseTXBSFmicroglianeural inflammationPS cDKOmouse modeltraditional Chinese herbal medicine research

references

LANE C A， HARDY J， SCHOTT J M. Alzheimer's disease［J］. Eur J Neurol， 2018， 25（1）： 59-70.

GANDY S， HEPPNER F L. Microglia as dynamic and essential components of the amyloid hypothesis［J］. Neuron， 2013， 78（4）： 575-577.

林水淼，王健，周如倩，等. 从心、肾论治阿尔茨海默病的临床研究［J］. 中国中西医结合杂志，2003， 23（8）： 583-586.

PRESTON A R， EICHENBAUM H. Interplay of hippocampus and prefrontal cortex in memory［J］. Curr Biol， 2013， 23（17）： R764-R773.

王迪霖，郎韫哲，袁见，等. 调心补肾方改善Presenilin1/2条件性双基因敲除小鼠记忆障碍的机制研究［J］. 世界科学技术-中医药现代化，2019， 21（9）： 1827-1834.

ZHAO Y， DENG H， LI K， et al. Trans-cinnamaldehyde improves neuroinflammation-mediated NMDA receptor dysfunction and memory deficits through blocking NF-κB pathway in presenilin1/2 conditional double knockout mice［J］. Brain Behav Immun， 2019， 82（1）： 45-62.

王健，尹兆宝，林水淼. 调神方对老年性痴呆大鼠学习记忆和细胞因子调节的实验研究［J］. 中国临床康复，2002， 6（7）： 964-965.

林水淼，杨柏灿，林松华. 对进行性隐匿型痴呆症的中医学研究［J］. 上海中医药杂志，1994， 28（10）： 9-11.

王健，林水淼. “心肾同治”阿尔茨海默病的思考［J］. 上海中医药杂志，2011， 45（9）： 22-23.

ENNERFELT H， LUKENS J. The role of innate immunity in Alzheimer's disease［J］. Immunol Rev， 2020， 297（1）： 225-246.

EIKELENBOOM P， VEERHUIS R， SCHEPER W， et al. The significance of neuroinflammation in understanding Alzheimer's disease［J］. J Neural Transm， 2006， 113（11）： 1685-1695.

CALSOLARO V， EDISON P. Neuroinflammation in Alzheimer's disease： Current evidence and future directions［J］. Alzheimers Dement， 2016， 12（6）： 719-732.

JIANG X， ZHANG D， SHI J， et al. Increased inflammatory response both in brain and in periphery in presenilin 1 and presenilin 2 conditional double knock-out mice［J］. J Alzheimers Dis， 2009， 18（3）： 515-523.

HAN W， JI T， WANG L， et al. Abnormalities in periodontal and salivary tissues in conditional presenilin 1 and presenilin 2 double knockout mice［J］. Mol Cell Biochem， 2011， 347（1）： 13-20.

FENG R， WANG H， WANG J， et al. Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2［J］. Proc Natl Acad Sci U S A， 2004， 101（21）： 8162-8167.

REGEN F， HELLMANN-REGEN J， COSTANTINI E， et al. Neuroinflammation and Alzheimer's disease： implications for microglial activation［J］. Curr Alzheimer Res， 2017， 14（11）： 1140-1148.

HANSEN D V， HANSON J E， SHENG M. Microglia in Alzheimer's disease［J］. J Cell Biol， 2018， 217（2）： 459-472.

PROKOP S， MILLER K R， HEPPNER F L. Microglia actions in Alzheimer’s disease［J］. Acta Neuropathologica， 2013， 126（4）： 461-477.

SARLUS H， HENEKA M T. Microglia in Alzheimer's disease［J］. J Clin Invest， 2017， 127（9）： 3240-3249.

王佳，张丽，隗和儒，等. 趋化因子和小胶质细胞在阿尔茨海默病神经炎症中的作用研究进展［J］. 中国比较医学杂志，2021，31（6）：139-147.

CACQUEVEL M， LEBEURRIER N， CHEENNE S， et al. Cytokines in neuroinflammation and Alzheimer's disease［J］. Curr Drug Targets， 2004， 5（6）： 529-534.

KAUR D， SHARMA V， DESHMUKH R. Activation of microglia and astrocytes： a roadway to neuroinflammation and Alzheimer's disease［J］. Inflammopharmacology， 2019， 27（4）： 663-677.

ROUZER C， MARNETT L. Structural and chemical biology of the interaction of cyclooxygenase with substrates and non-steroidal anti-inflammatory drugs［J］. Chem Rev， 2020， 120（15）： 7592-7641.

SASAKI T， KITAGAWA K， YAMAGATA K， et al. Amelioration of hippocampal neuronal damage after transient forebrain ischemia in cyclooxygenase-2-deficient mice［J］. J Cereb Blood Flow Metab， 2004， 24（1）： 107-113.

Views

389

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of Shenling Baizhu Powder on intestinal mucosal barrier in mice with xenograft model of colorectal cancer after chemotherapy

Study on effects of Tiaoxin Bushen Formula on improving synapse loss and tau hyperphosphory⁃lation in prefrontal cortex of Alzheimer’s disease mice

Effect of astragaloside Ⅳ on microglia activity in Alzheimer’s disease rats based on MEK5/ERK5 signaling pathway

Effects of Xinqian Ganjie Decoction on lncRNA SNHG16， EGFR and MUC5AC mRNA expression in chronic rhinosinusitis mice

Mechanism of Yucan Granules improving podocyte damage and treating diabetic nephropathy

Related Author

No data

Related Institution

Department of Traditional Chinese Medicine Oncology， Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Department of Pneumology， Zhongshan Hospital， Fudan University

Department of Pneumology， Xuhui District Central Hospital

Department of Traditional Chinese Medicine， Xuhui District Central Hospital

Department of Neurology, The First Affiliated Hospital of Henan University

⁰