STAT3-mediated polarization of A2 phenotype astrocytes alleviates painful diabetic peripheral neuropathy in type 1 diabetic rats
10.16352/j.issn.1001-6325.2025.07.0889
- VernacularTitle:STAT3介导A2表型星形胶质细胞极化缓解1型糖尿病大鼠周围神经痛
- Author:
Tingting FAN
1
;
Huili LI
;
Ruijuan GUO
;
Danxu MA
;
Yun WANG
Author Information
1. 首都医科大学附属北京友谊医院 麻醉科,北京 100050
- Keywords:
type 1 diabetic mellitus(T1DM);
painful diabetic neuropathy(PDN);
signal transducer and activator of transcription 3(STAT3);
A2 phenotype reactive astrocytes
- From:
Basic & Clinical Medicine
2025;45(7):889-896
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of STAT3 over-expression-mediated A2 astrocyte polarization on type 1 diabetic mellitus(T1DM)peripheral neuropathy.Methods STAT3 over-expression virus was intrathecally injected into type 1 diabetic rats with painful diabetic neuropathy(PDN).The rats were divided into four groups:control group,T1DM group,T1DM+vector group,and T1DM+STAT3 OE group.Paw withdrawal threshold and paw withdrawal latency were measured.Flow cytometry and RT-qPCR were used to sort astrocytes and determine the phenotype of reactive astrocytes.Immune-fluorescence staining microscopy was performed to observe the changes of A2 phenotype astrocytes in the spinal dorsal horn of each group.Results Compared to the control group,the me-chanical(P＜0.001)and heat thresholds(P＜0.05)were significantly reduced in the T1DM group.The mechanical threshold was significantly increased in the T1DM+STAT3 OE group as compared to that in the T1DM group(P＜0.001).Histolgical analysis showed degenerative pathological changes of spinal dorsal horn astrocytes in the T1DM group.Astrocytes in the T1DM+STAT3 OE group were activated and polarized toward the A2 phenotype.Conclusions The STAT3 pathway in the spinal dorsal horn astrocytes of rats with type 1 diabetic neuropathy is im-paired.Restoring STAT3 expression promotes activation of astrocyte proliferation,activation,and polarization toward the A2 phenotype,thereby alleviating diabetic neuropathic pain.
