重明益损汤调控EGFR/STAT3信号通路改善TON大鼠视功能的实验研究OA

OBJECTIVE To observe the effects and mechanism of Chongming Yisun Decoction on rats with traumatic optic neuropathy(TON).METHODS A total of 25 rats were used to establish a TON model via lateral quantitative traction of the optic nerve.They were randomly divided into a model group(MG),and low,medium,and high dose Chongming Yisun Decoction groups(CMYS-L,CMYS-M,CMYS-H).The rats undergoing sham surgery were designated as the sham group(Sham),with five rats in each group.Seven days before modeling,retinal ganglion cell(RGC)in the Sham and MG groups were retrogradely labeled with Fluoro-Gold.Seven days post-modeling,RGC counts were performed under a fluorescence microscope to validate the model.The rats of CMYS-L,CMYS-M,and CMYS-H groups were administered Chongming Yisun Decoction at doses of 5.5 g/kg,11 g/kg,and 22 g/kg,respectively,by gavage.The rats of the Sham and MG groups received an equal volume of distilled water.Administration continued for 14 consecutive days.After treatment,flash visual evoked potentials(F-VEP)were recorded to assess visual function.Immunofluorescence staining was used to observe the number of brain-specific homeobox protein 3A(Brn3a)-positive cells and the expression of glial fibrillary acidic protein(GFAP)in the retina.Western Blot was employed to detect the expression of epidermal growth factor receptor(EGFR)and signal transducer and activator of transcription 3(STAT3)pathway proteins in the retina.RESULTS(1)Model validation:The RGC density and RGC labeling rate in the left eyes of the MG group were lower than those in the Sham group,the differences were all statistically significant(both P<0.05).(2)F-VEP:The N1-P1 and N2-P2 amplitudes in the MG group were lower,and the P2 latency was higher than those in the Sham group;The N1-P1 and N2-P2 amplitudes in the CMYS-M and CMYS-H groups were higher,and the P2 latency was lower than those in the MG group,the differences were all statistically significant(all P<0.05).(3)Brn3a:The count of Brn3a-positive RGC in the MG group was lower than that in the Sham group,while counts in the CMYS-M and CMYS-H groups were higher than those in the MG group,the differences were all statistically significant(all P<0.05).(4)GFAP:GFAP expression in the retina of the MG group was higher than that in the Sham group,while expression in the CMYS-L,CMYS-M,and CMYS-H groups was lower than that in the MG group,the differences were all statistically significant(all P<0.05).(5)EGFR/STAT3:The expression of EGFR and p-STAT3 proteins in the retina of the MG group was higher than that in the Sham group;EGFR protein expression in the CMYS-L,CMYS-M,and CMYS-H groups was lower than that in the MG group;The expression of p-STAT3 protein in the CMYS-M and CMYS-H groups was lower than that in the MG group,the differences were all statistically significant(all P<0.05).CONCLUSIONS Chongming Yisun Decoction has a protective effect against optic nerve injury in rats.Its mechanism may be related to inhibiting the expression of EGFR and p-STAT3 proteins in the retina,thereby alleviating the excessive activation of reactive astrocytes and protecting RGC.