周细胞脱失与神经精神性狼疮血瘀证目征和血脑屏障功能障碍的相关性

doi:10.3969/j.issn.1006-5725.2025.06.003

Abstract

Abstract:

Objective This study aims to investigate the pathological role and molecular mechanisms of pericyte depletion in neuropsychiatric lupus （NPSLE） and to assess the potential of the PDGFR-β signaling pathway as a novel therapeutic target for NPSLE. Methods NPSLE models were established using 8-week-old female MRL/lpr mice， from which those exhibiting abnormal behaviors were selected for further analysis. The PDGFR-β signaling pathway was modulated using an agonist to promote pericyte proliferation or an inhibitor to suppress pericyte apoptosis. The effects of these treatments on blood-brain barrier （BBB） integrity， eye-signs in blood stasis syndrome， neuronal integrity， and tight junction protein expression were evaluated. Evans blue staining， H&E staining， Nissl staining， and immunofluorescence staining were employed to assess the expression of tight junction proteins （Cadherin， ZO-1）， endothelial cell markers （CD31）， and pericyte markers （NG2）. Results Mice in the NPSLE group exhibited significant anxiety， depression， and cognitive impairment. In the PDGFR-β inhibition group， eye-signs in blood stasis syndrome scores were significantly elevated （P < 0.01）， BBB permeability was markedly increased （P < 0.001）， neuronal numbers were significantly reduced， tight junction protein expression was diminished， and pericyte depletion was aggravated. Conversely， the PDGFR-β agonist group showed a significant reduction in eye-signs in blood stasis syndrome scores （P < 0.01）， improved pericyte survival， enhanced expression of tight junction proteins， reduced neuronal damage， and restoration of BBB function （P < 0.001）. Immunofluorescence staining further confirmed that PDGFR-β activation significantly protected pericytes. Conclusions Pericyte depletion is closely associated with increased BBB permeability and exacerbation of eye-signs in blood stasis syndrome. Modulation of the PDGFR-β signaling pathway may provide a promising therapeutic strategy for NPSLE.

Key words: pericytes, neuropsychiatric systemic lupus erythematosus, eye-signs in blood stasis syndrome, blood-brain barrier

CLC Number:

R747.9

Jianbin LI,Rui. WU. Correlation study on pericyte depletion， eye⁃signs in blood stasis syndrome， and blood⁃brain barrier dysfunction in neuropsychiatric systemic lupus erythematosus[J]. The Journal of Practical Medicine, 2025, 41(6): 790-799.

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References 26

1	张索，刘冬舟. 系统性红斑狼疮脑病的研究进展［J］. 实用医学杂志， 2020， 36（3）： 414-419.
2	SCHWARTZ N， STOCK A D， PUTTERMAN C. Neuropsychiatric lupus： New mechanistic insights and future treatment directions［J］. Nat Rev Rheumatol， 2019，15（3）： 137-152. doi:10.1038/s41584-018-0156-8 doi: 10.1038/s41584-018-0156-8
3	申杰，徐桂华. 阿尔茨海默病与血脑屏障的相关性研究进展［J］. 实用医学杂志， 2024， 40（11）： 1602-1606.
4	SANTOS G S P， PRAZERES P H D M， MINTZ A， et al. Role of pericytes in the retina［J］. Eye （Lond）， 2018，32（3）： 483-486. doi:10.1038/eye.2017.220 doi: 10.1038/eye.2017.220
5	KURELI G， YILMAZ-OZCAN S， ERDENER S E， et al. F-actin polymerization contributes to pericyte contractility in retinal capillaries［J］. Exp Neurol， 2020， 332： 113392. doi:10.1016/j.expneurol.2020.113392 doi: 10.1016/j.expneurol.2020.113392
6	HUANG H. Pericyte-Endothelial Interactions in the Retinal Microvasculature［J］. Int J Mol Sci， 2020， 21（19）： 7413. doi:10.3390/ijms21197413 doi: 10.3390/ijms21197413
7	NIKOLAKOPOULOU A， MONTAGNE A， et al. Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss［J］. Nat Neurosci， 2019， 22： 1089-1098. doi:10.1038/s41593-019-0434-z doi: 10.1038/s41593-019-0434-z
8	SHI H， KORONYO Y， RENTSENDORJ A， et al. Identification of early pericyte loss and vascular amyloidosis in Alzheimer disease retina［J］. Acta Neuropathol， 2020， 139： 813-836. doi:10.1007/s00401-020-02134-w doi: 10.1007/s00401-020-02134-w
9	SWEENEY M D， AYYADURAI S， ZLOKOVIC B V. Pericytes of the neurovascular unit： Key functions and signaling pathways［J］. Nat Neurosci， 2016， 19（6）： 771-783. doi:10.1038/nn.4288 doi: 10.1038/nn.4288
10	HIRUNPATTARASILP C， ATTWELL D， FREITAS F. The role of pericytes in brain disorders： From the periphery to the brain［J］. J Neurochem， 2019， 150： 648-665. doi:10.1111/jnc.14725 doi: 10.1111/jnc.14725
11	HAN X， XU T， DING C， et al. Neuronal NR4A1 deficiency drives complement-coordinated synaptic stripping by microglia in a mouse model of lupus［J］. Signal Transduct Target Ther， 2022， 7（1）： 47-56. doi:10.1038/s41392-021-00867-y doi: 10.1038/s41392-021-00867-y
12	赖琴，郭雪，王梅英. 系统性红斑狼疮动物模型及研究进展［J］. 中国实验动物学报， 2024， 32（11）： 1493-1504.
13	TOMALLA V， SCHMEISSER M J， WEINMANN-MENKE J. Mouse models， antibodies， and neuroimaging： Current knowledge and future perspectives in neuropsychiatric systemic lupus erythematosus （NPSLE）［J］. Front Psychiatry， 2023， 14： 1078607. doi:10.3389/fpsyt.2023.1078607 doi: 10.3389/fpsyt.2023.1078607
14	WU C， YANG L， LI Y， et al. Effects of exercise training on anxious-depressive-like behavior in Alzheimer rat［J］. Med Sci Sports Exerc， 2020， 52（7）： 1456-1469. doi:10.1249/mss.0000000000002294 doi: 10.1249/mss.0000000000002294
15	GERANMAYEH M H， RAHBARGHAZI R， FARHOUDI M. Targeting pericytes for neurovascular regeneration［J］. Cell Commun Signal， 2019， 17（1）： 26. doi:10.1186/s12964-019-0340-8 doi: 10.1186/s12964-019-0340-8
16	OTA Y， SRINIVASAN A， CAPIZZANO A A， et al. Central nervous system systemic lupus erythematosus： Pathophysiologic， clinical， and imaging features［J］. Radiographics， 2022， 42（1）： 212-232. doi:10.1148/rg.210045 doi: 10.1148/rg.210045
17	PERSIDSKY Y， HILL J， ZHANG M， et al. Dysfunction of brain pericytes in chronic neuroinflammation［J］. J Cereb Blood Flow Metab， 2016， 36（4）： 794-807. doi:10.1177/0271678x15606149 doi: 10.1177/0271678x15606149
18	SMYTH L C， RUSTENHOVEN J， PARK T I H， et al. Unique and shared inflammatory profiles of human brain endothelia and pericytes［J］. J Neuroinflammation， 2018， 15： 138. doi:10.1186/s12974-018-1167-8 doi: 10.1186/s12974-018-1167-8
19	KIM Y， LEE S， ZHANG H， et al. CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation［J］. J Neuroinflammation， 2020， 17（1）： 48. doi:10.1186/s12974-020-1727-6 doi: 10.1186/s12974-020-1727-6
20	CHEN X， XUE J， ZOU J， et al. Resveratrol alleviated neuroinflammation induced by pseudorabies virus infection through regulating microglial M1/M2 polarization［J］. Biomed Pharmacother， 2023， 160： 114271. doi:10.1016/j.biopha.2023.114271 doi: 10.1016/j.biopha.2023.114271
21	LI W， NIU X， DAI Y， et al. Rnf-213 knockout induces pericyte reduction and blood-brain barrier impairment in mouse［J］. Mol Neurobiol， 2023， 60（11）： 6188-6200. doi:10.1007/s12035-023-03480-y doi: 10.1007/s12035-023-03480-y
22	LIU G， WANG J， WEI Z， et al. Elevated PDGF-BB from bone impairs hippocampal vasculature by inducing PDGFRβ shedding from pericytes［J］. Adv Sci （Weinh）， 2023， 10（20）： e2206938. doi:10.1002/advs.202206938 doi: 10.1002/advs.202206938
23	SHI H， KORONYO Y， RENTSENDORJ A， et al. Identification of early pericyte loss and vascular amyloidosis in Alzheimer's disease retina［J］. Acta Neuropathol， 2020， 139（5）： 813-836. doi:10.1007/s00401-020-02134-w doi: 10.1007/s00401-020-02134-w
24	KVERNEBO A K， MIYAMOTO T， SPORAST A H， et al. Quantification of ocular surface microcirculation by computer-assisted video microscopy and diffuse reflectance spectroscopy［J］. Exp Eye Res， 2020， 201： 108312. doi:10.1016/j.exer.2020.108312 doi: 10.1016/j.exer.2020.108312
25	ZHAO S， YANG Z， SUN P， et al. Conjunctival microcirculation is associated with cerebral cortex microcirculation in post-resuscitation mild hypothermia： A rat model［J］. Microcirculation， 2020， 27（3）： e12604. doi:10.1111/micc.12604 doi: 10.1111/micc.12604
26	SHI L H， LIU Z Y， YU S J， et al. Performance of eye sign combined with increased interleukin-6 in cerebrospinal fluid in patients with neuropsychiatric lupus erythematosus［J］. Int J Rheum Dis， 2023， 26（8）： 1464-1473. doi:10.1111/1756-185x.14731 doi: 10.1111/1756-185x.14731

项目	NPSLE组（n = 6）	PDGFR-β激动组（n = 6）	P值	NPSLE对照组（n = 6）	PDGFR-β抑制组（n = 6）	P值
血管扩张			0.092			0.011
0分	0	0		4（66.7）	3（50）
5分	1（16.7）	4（66.7）		2（33.3）	3（50）
10分	5（83.3）	2（33.3）		0	0
血管扭曲			0.049			0.002
0分	0	0		6（100）	0
5分	3（50）	6（100）		0	4（66.7）
10分	3（50）	0		0	2（33.3）
出血点			0.145			0.341
0分	4（66.7）	6（100）		6（100）	5（83.3）
5分	2（33.3）	0		0	1（16.7）
10分	0	0		0	0

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Correlation study on pericyte depletion， eye⁃signs in blood stasis syndrome， and blood⁃brain barrier dysfunction in neuropsychiatric systemic lupus erythematosus

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