收藏切换
Exploring Effect of Buzhong Yiqi Decoction(补中益气汤)on Abnormal Autophagy of Hippocampal Neurons in Autoimmune Thyroiditis Model Mice Based on miR-190b/PHLPP1/AKT/FOXO3a Pathway
收藏切换
PDF
Xiaowei LIU1, 2, Tianshu GAO3
Chinese Archives of Traditional Chinese Medicine | 2025, 43(12) : 60 - 67
Less
收藏切换
Chinese Archives of Traditional Chinese Medicine | 2025, 43(12): 60-67
Target on National Project
Exploring Effect of Buzhong Yiqi Decoction(补中益气汤)on Abnormal Autophagy of Hippocampal Neurons in Autoimmune Thyroiditis Model Mice Based on miR-190b/PHLPP1/AKT/FOXO3a Pathway
Full
Xiaowei LIU1, 2, Tianshu GAO3
Affiliations
  • 1.Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China
  • 2.The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China
  • 3.Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China
Published: 2025-12-10 doi: 10.13193/j.issn.1673-7717.2025.12.010
Outline
收藏切换
Objective

To explore the effect of Buzhong Yiqi Decoction(补中益气汤)on abnormal autophagy of hippocampal neurons in autoimmune thyroiditis(AIT)modelmice based on themiR-190b/Pleckstrin homology domain leucine-rich repeat protein phosphatase(PHLPP1)/protein kinase B(AKT)/Forkhead BoxO3a(FOXO3a)pathway.

Method

Fifty female NOD.H-2h4 mice were randomly divided into blank control group(CG group),model group(MG group),low,medium and high dose groups of Buzhong Yiqi Decoction(BG-1,BG-2,BG-3 groups),with 10 mice in each group.The AITmodelwas established through pig thyroglobulin inductionmethod.After successfulmodeling,the BG-1,BG-2 and BG-3 groups were given 2.73,8.19 and 24.57 g/(kg·d)Buzhong Yiqi Decoction by gavage,respectively.The CG and MG groups were given an equal amount of distilled water by gavage,with a rest of1 day every 6 days for 8 consecutive weeks.Morriswatermaze experiment was used to test the spatial learning and memory abilities of mice.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of serum triiodothyronine(T3),tetraiodothyronine(T4),thyroid stimulating hormone(TSH)and thyroglobulin antibody(TgAb)in mice.Hematoxylin eosin(HE)stainingmethod was used to observe the morphological changes of mouse thyroid tissue.Transmission electron microscopy was used to observe the ultrastructure of hippocampal neurons in mice.Immunofluorescence staining was used to observe the positive expression of LC3 in the hippocampal CA1 region of mouse brain tissue.Reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expressions ofmiR-190b-5p and PHLPP1 mRNA in mouse hippocampal tissue.The Wes fully automated Western blot quantitative analysis system detected the protein levels of Beclin1,LC3,P62,PHLPP1,AKT,p-AKT,FOXO3a and p-FOXO3a inmouse hippocampal tissue.The dual luciferase reporter gene experiment confirmed the targeting relationship bet weenmiR-190b-5p and PHLPP1.

Results

Compared with those of the CG group,the escape latency of MG group was significantly prolonged(P<0.01),and the number of crossing platforms and target quadrant residence time were significantly reduced(P<0.01).The serum TgAb content significantly increased(P<0.01).The size of thyroid follicles varies,and there was a large amount of lymphocyte infiltration in the stroma of follicles and damaged hippocampal neuronal structure with the appearance of autophagosomes.The average fluorescence intensity of LC3 in hippocampal CA1 region increased(P<0.01).The expression levels of Beclin1,LC3,PHLPP1 and FOXO3a proteins in hippocampal tissue increased,while the expression levels of P62,p-AKT/AKT and p-FOXO3a/FOXO3a proteins decreased(P<0.01).ThemiR-190b-5p level in hippocampal tissue decreased,while the PHLPP1mRNA level increased(P<0.01).Compared with the MG group,the BG-1,BG-2 and BG-3 groups significantly shortened the escape latency ofmice(P<0.05,P<0.01),and increased the number of times they crossed the platform and the target quadrant residence time(P<0.01).The structure of thyroid follicular epithelial cells was relatively intact,and the infiltration of lymphocytes significantly improved.The morphology and structure of hippocampalneurons recovered,and autophagosomes decreased.The average fluorescence intensity of LC3 in hippocampal CA1 region decreased(P<0.01).The expression levels of Beclin1,LC3,PHLPP1 and FOXO3a proteins in mouse hippocampal tissue decreased,while the expression levels of P62,p-AKT/AKT and p-FOXO3a/FOXO3a proteins increased(P<0.05,P<0.01).ThemiR-190b-5p level in hippocampal tissue increased,while the PHLPP1 mRNA level significantly decreased(P<0.05,P<0.01).The dual luciferase assay confirmed that PHLPP1 was a targeted regulatorymolecule of miR-190b-5p.

Conclusion

Buzhong Yiqi Decoction may improve abnormal autophagy in hippocampal neurons of AITmice by regulating themiR-190b/PHLPP1/AKT/FOXO3a signaling pathway,thereby reducing hippocampal neuronal damage and alleviating cognitive dysfunction.

autoimmune thyroiditis  /  cognitive impairment  /  Buzhong Yiqi Decoction(补中益气汤)  /  autophagy  /  MiR-190b  /  PHLPP1/AKT/FOXO3a
Xiaowei LIU, Tianshu GAO. Exploring Effect of Buzhong Yiqi Decoction(补中益气汤)on Abnormal Autophagy of Hippocampal Neurons in Autoimmune Thyroiditis Model Mice Based on miR-190b/PHLPP1/AKT/FOXO3a Pathway[J]. Chinese Archives of Traditional Chinese Medicine, 2025 , 43 (12) : 60 -67 . DOI: 10.13193/j.issn.1673-7717.2025.12.010
Year 2025 volume 43 Issue 12
PDF
56
29
Cite this Article
BibTeX
Article Info
doi: 10.13193/j.issn.1673-7717.2025.12.010
  • Online Date:2026-04-29
  • Published:2025-12-10
Article Data
Affiliations
History
Funding
Affiliations
    1.Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China
    2.The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China
    3.Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,Liaoning,China
References
Share
https://castjournals.cast.org.cn/joweb/zhzyyxk/EN/10.13193/j.issn.1673-7717.2025.12.010
Share to
QR

Scan QR to access full text

Cite this article
BibTeX
Citations
表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
  • BibTeX
  • EndNote
  • RefWorks
  • TxT