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 mechanical (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 impaired. Restoring STAT3 expression promotes activation of astrocyte proliferation, activation, and polarization toward the A2 phenotype, thereby alleviating diabetic neuropathic pain.

Key words: type 1 diabetic mellitus (T1DM), painful diabetic neuropathy (PDN), signal transducer and activator of transcription 3 (STAT3), A2 phenotype reactive astrocytes