Huanglian Jiedutang Improves Myelin Damage and Agitated Behavior in Vascular Dementia by Regulating Microglial Polarization via CD22/SHP-1/p-Akt Signaling Pathway
10.13422/j.cnki.syfjx.20251495
- VernacularTitle:黄连解毒汤通过CD22/SHP-1/p-Akt信号通路调控小胶质细胞表型改善血管性痴呆髓鞘损伤和激越行为
- Author:
Chen CHEN
1
;
Xiaoxia FENG
1
;
Shiting LIANG
2
;
Xinxian SHI
2
;
Guang YANG
3
;
Jing QIU
3
Author Information
1. The First Clinical Medical School，Hubei University of Chinese Medicine，Wuhan 430061，China
2. Clinical College of Traditional Chinese Medicine（TCM），Hubei University of Chinese Medicine， Wuhan 430061，China
3. Hubei Provincial Hospital of TCM，Wuhan 430061，China
- Publication Type:Journal Article
- Keywords:
Huanglian Jiedutang;
microglia;
myelin injury;
vascular dementia;
agitation-like behavior
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(2):25-33
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanisms by which Huanglian Jiedutang （HLJDT） modulates microglial （MG） phenotypes through the sialic acid-binding Ig-like lectin 2 （SIGLEC2/CD22）/Src-homology-2-domain-containing protein tyrosine phosphatase-1 （SHP-1）/phosphorylated protein kinase B （p-Akt） signaling pathway， thereby promoting myelin repair and alleviating agitation-like behaviors in vascular dementia （VAD）. MethodsSixty C57BL/6J mice were randomly assigned to a sham （normal） group， model group， HLJDT low-， medium-， and high-dose groups （2.5， 5， and 10 g·kg-1·d-1）， and a risperidone group （2 mg·kg-1·d-1）， with 10 mice per group. VAD was induced by bilateral common carotid artery stenosis （BCAS）. From day 42， mice received drug interventions for 2 weeks. Agitation-like behaviors were assessed using the resident-intruder test. After behavioral testing， ventrolateral part of the ventromedial hypothalamus （VMHvl） tissues were collected. Western blot was used to measure protein levels of myelin oligodendrocyte glycoprotein （MOG）， myelin basic protein （MBP）， proteolipid protein （PLP）， inducible nitric oxide synthase （iNOS）， arginase-1 （Arg1）， CD86， CD206， and CD22， SHP-1， and p-Akt. Immunofluorescence was used to evaluate myelin-associated glycoprotein （MAG） intensity and the proportion of iNOS+/ionized calcium-binding adapter molecule 1 （Iba1）+ cells. ELISA was used to detect tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β. ResultsCompared with the normal group， the model group exhibited markedly increased biting and aggressive behaviors and shortened attack latency （P<0.01）. MOG， MBP， and PLP protein levels and MAG fluorescence intensity were significantly reduced （P<0.05， P<0.01）. INOS and CD86 expression and TNF-α， IL-6， and IL-1β levels were significantly elevated （P<0.01）. CD22 and SHP-1 expression increased significantly （P<0.01）， whereas p-Akt expression decreased （P<0.01）. Compared with the model group， the medium- and high-dose HLJDT groups and the risperidone group showed markedly reduced biting and aggression （P<0.05， P<0.01） and prolonged attack latency （P<0.01）. MOG， MBP， and PLP levels and MAG fluorescence intensity were significantly increased （P<0.05， P<0.01）. INOS， CD86， TNF-α， IL-6， and IL-1β levels decreased significantly （P<0.05， P<0.01）. CD22 and SHP-1 expression decreased， while p-Akt expression increased significantly （P<0.05， P<0.01）. ConclusionHLJDT may modulate CD22/SHP-1/p-Akt signaling in the VMHvl， promote the shift of MG toward an anti-inflammatory and phagocytic phenotype， enhance myelin repair， and improve agitation-like behaviors in VAD mice.
