眼科新进展2025，Vol.45Issue(6)：440-446,7.DOI:10.13389/j.cnki.rao.2025.0077
GPR110配体对糖尿病小鼠视网膜神经炎症的影响
Effect of GPR110 ligand on retinal neuroinflammation in diabetes mice
摘要
Abstract
Objective To investigate the effect of a G-protein receptor 110(GPR110)ligand on retinal neuroinflam-mation in diabetic mice by regulating the Janus kinase 2/signal transduction and activator of transcription 3(JAK2/STAT3)signaling pathway.Methods This experiment was divided into two parts.(1)Twelve C57BL/6J mice(24 eyes)were randomly divided into the control group,4-week streptozotocin(STZ)induction(STZ4-week)group,STZ 8-week group,and STZ 12-week group,with 3 mice in each group.The diabetic model was induced by intraperitoneal injection of STZ(150 mg·kg-1)in all groups except the control group.The expression of GPR110 and glutamine synthetase(GS)in the retinal tissue of mice was detected by immunofluorescence staining to screen the optimal acting time.(2)Thirty-two C57BL/6J mice(64 eyes)were divided into the control group,STZ 8-week group,the STZ+N-docosahexaenol ethanola-mine(SYN)group,and the STZ+SYN+adeno-associated virus-mediated GPR110(AAV-GPR110)group,with 8 mice in each group,and they were subjected to corresponding treatment.Immunohistochemistry was performed to detect the ex-pression of glial fibrillary acidic protein(GFAP)in mouse retinal tissues.ELISA was performed to detect the level of inter-leukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in mouse retinal tissues.Western blot was performed to detect the ratio of JAK2 to phosphorylated JAK2(p-JAK2)and that of STAT3 to phosphorylated STAT3(p-STAT3).Results(1)GPR110 in the retina of mice in the STZ 4-week group,STZ 8-week group,and STZ 12-week group was mainly expressed in Müller cells.The highest expression intensity of GPR110 was observed in the retina of mice in the STZ 8-week group;therefore,the diabetic mice in the STZ 8-week group were selected for subsequent experiments.(2)Compared with the control group,mice in the STZ 8-week group and the STZ+SYN+AAV-GPR110 group exhibited a decrease in the retinal thickness and the number of retinal ganglion cells,those in the STZ+SYN group displayed a de-crease in the retinal thickness(all P＜0.05),and those in the other three groups presented a significant increase in the in-tensity of GFAP-positive expression and an increase in the level of IL-6,IL-1β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Compared with the STZ 8-week group,the retinal thickness and the number of retinal ganglion cells in the STZ+SYN group increased,the intensity of GFAP-positive expression decreased,and the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values decreased(all P＜0.05).Compared with the STZ+SYN group,mice in the STZ+SYN+AAV-GPR110 group showed a decrease in the retinal thickness and the number of retinal ganglion cells,a significant increase in the intensity of GFAP-positive expression,and an increase in the level of IL-6,IL-1 β,and TNF-α and the p-JAK2/JAK2 and p-STAT3/STAT3 values(all P＜0.05).Conclusion The GPR110 ligand could alleviate retinal neuroinflammation in diabetic mice by inhibiting the JAK2/STAT3 signaling pathway.关键词
G蛋白偶联受体110/糖尿病视网膜病变/Müller细胞/神经炎症/JAK2/STAT3信号通路Key words
G-protein receptor 110/diabetic retinopathy/Müller cells/neuroinflammation/JAK2/STAT3 signaling pathway分类
医药卫生引用本文复制引用
李春桃,左中夫,匙也..GPR110配体对糖尿病小鼠视网膜神经炎症的影响[J].眼科新进展,2025,45(6):440-446,7.基金项目
辽宁省自然科学基金资助计划项目(编号:2023-MS-312) （编号:2023-MS-312）
辽宁省教育厅面上项目(编号:LJKMZ20221241) （编号:LJKMZ20221241）
锦州医科大学教育教学研究与改革项目(编号:YB2023019,YB2024020) （编号:YB2023019,YB2024020）
