Qihuang Jianpi Zishen Granules improves thrombocytopenia in mice with systemic lupus erythematosus by suppressing platelet autophagy via the Ca2+/CaMKK2/AMPK/mTOR signaling pathway.
10.12122/j.issn.1673-4254.2024.12.08
- Author:
Yunfei LI
1
;
Lijun PANG
1
;
Longwu SHU
1
;
Ming LI
1
;
Chuanbing HUANG
1
Author Information
1. Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
- Publication Type:Journal Article
- Keywords:
Ca 2+/CaMKK2/AMPK/mTOR signaling pathway;
Qihuang Jianpi Zishhen Granules;
platelet autophagy;
systemic lupus erythematosus
- MeSH:
Animals;
Lupus Erythematosus, Systemic/metabolism*;
Mice;
Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism*;
Drugs, Chinese Herbal/pharmacology*;
TOR Serine-Threonine Kinases/metabolism*;
Thrombocytopenia/metabolism*;
Signal Transduction/drug effects*;
Autophagy/drug effects*;
AMP-Activated Protein Kinases/metabolism*;
Disease Models, Animal;
Mice, Inbred C57BL;
Mice, Inbred MRL lpr;
Calcium/blood*;
Blood Platelets/metabolism*
- From:
Journal of Southern Medical University
2024;44(12):2327-2334
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the mechanism of Qihuang Jianpi Zishen Granules (QJZG) for improving thrombocytopenia in a mouse model of systemic lupus erythematosus (SLE).
METHODS:Twenty-four MRL/lpr lupus mice were randomized equally into 4 groups for treatment with daily gavage of saline, QJZG or prednisone (Pred) or intraperitoneal injection (twice a week) of CaMKK2 activator, with 6 C57BL/6 mice with saline gavage as the control group. After 8 weeks of treatment, the mice were examined for PLT, PCT, PDW, MPV, serum levels of TPO, IL-6, IL-10, TNF-α and IFN-γ, and calcium ion fluorescence intensity using ELISA or flow-through assay. RT-qPCR was used to detect platelet CaMKK2, AMPK2α, mTOR, Beclin1 and p62 mRNA expression levels, and the protein expressions of CaMKK2, p-CaMKK2, AMPK, p-AMPK, mTOR, p-mTOR, LC3, Beclin1 and p62 were detected using Western blotting.
RESULTS:The saline-treated MRL/lpr lupus mice showed significantly lowered levels of PLT, PCT, IL-10, mTOR, p62 mRNA, p-mTOR and P62 with increased PDW, MPV, serum TPO, IL-6, TNF-α and IFN-γ levels, and platelet expressions of CaMKK2, AMPK, Bcl-1 mRNA, p-CaMKK2, p-AMPK, LC3II and Beclin1. These abnormalities were significantly improved in QJZG group and Pred group but worsened after treatment with the CaMKK2 activator.
CONCLUSIONS:QJZG can ameliorate thrombocytopenia in mouse models of SLE by reducing inflammation and inhibiting platelet autophagy via regulating the Ca2+/CaMKK2/AMPK/mTOR signaling pathways.
