甘肃中医药大学学报2025，Vol.42Issue(6)：1-8,8.DOI:10.16841/j.issn1003-8450.2025.06.01
益景汤干预糖尿病模型大鼠视网膜微血管损害机制研究
Mechanism of Yijing Tang(益景汤)in intervening retinal microvascular damage in diabetic model rats
摘要
Abstract
Objective To investigate the protective effect and mechanism of Yijing Tang(益景汤)on retinal microvascular damage in diabetic model rats.Methods 60 male rats of cleaning grade were randomly divided into four groups(15 rats each):normal group,model group,minocycline group,and Yijing Tang group.Diabetes mellitus(DM)rat models were established using streptozotocin(STZ).After successful model induction,the minocycline group and Yijing Tang group received respective intragastric interventions,while the normal group and model group were administered distilled water.After 16 weeks of intervention,all rats were euthanized.Retinal microvascular morphology was observed using periodic acid-schiff(PAS)staining,vascular permeability was assessed via Evans Blue(EB)method,and apoptosis of retinal microvascular pericytes(RMPs)and endothelial cells(ECs)was detec-ted by TUNEL method.Ultrastructural changes in the microvascular basement membrane were observed using elec-tron microscopy.Immunohistochemistry(IHC)measured the protein expression of matrix metalloproteinase 2(MMP-2)and tissue inhibitor of matrix metalloproteinase 2(TIMP-2)in retinal tissues.Western blotting quantified the relative expression of vascular endothelial growth factor A(VEGF-A)and urokinase-type plasminogen activator(uPA),while reverse transcription-polymerase chain reaction(RT-PCR)evaluated cysteine aspartate specific protease 3(Caspase-3)mRNA levels in retinal tissues.Results The model group exhibited compromised inner blood-retinal barrier(iBRB),with blurred capillary traces,fluorescent leakage,and thickened uneven microvascular basement membranes.Both Yijing Tang and minocycline groups showed mild iBRB damage,minor focal fluorescent leakage,and the basement membrane of retinal microvasculature was generally thickened and unevenly thick,but with im-provement compared to the model group.Compared with the normal group,the model group exhibited a significant increase in RMPs apoptosis(P＜0.05).Both the minocycline and Yijing Tang groups showed markedly reduced in RMPs apoptosis compared to the model group(P＜0.05).In retinal tissues,MMP-2 positive signals were significant-ly enhanced in the model,minocycline,and Yijing Tang groups.However,the Yijing Tang group displayed weaker MMP-2 staining intensity compared to the model group.TIMP-2 signals were faintly positive across all four groups,with no significant differences in staining intensity.The relative expression levels of uPA,VEGF-A proteins,and Caspase-3 mRNA were significantly upregulated in the model group versus the normal group(P＜0.05).In contrast,the Yijing Tang group demonstrated downregulated expression of these biomarkers compared to the model group(P＜0.05).Conclusion The therapeutic mechanism of Yijing Tang against DM-induced retinal microvascular damage may involve suppressing VEGF-A,uPA proteins,and Caspase-3 mRNA expression,regulating the MMP-2/TIMP-2 ratio,and alleviating microvascular leakage.关键词
糖尿病视网膜病变/益景汤/视网膜微血管损害/半胱天冬氨酸特异性蛋白酶3/血管内皮生长因子A/尿激酶型纤溶酶原激活剂/基质金属蛋白酶2/金属蛋白酶组织抑制剂2/大鼠分类
医药卫生引用本文复制引用
刘光辉,邱心悦,赵利,王丽,孟春,邹月兰,任秉仪..益景汤干预糖尿病模型大鼠视网膜微血管损害机制研究[J].甘肃中医药大学学报,2025,42(6):1-8,8.基金项目
国家自然科学基金面上项目(81774369) （81774369）
福建省自然科学基金卫生联合项目(2023J01852,2022J01352). （2023J01852,2022J01352）
