首页|期刊导航|郑州大学学报(医学版)|小檗碱对糖尿病视网膜病变大鼠视网膜巨噬细胞糖酵解及M2型极化的影响

小檗碱对糖尿病视网膜病变大鼠视网膜巨噬细胞糖酵解及M2型极化的影响OA

Effects of berberine on retinal macrophage glycolysis and M2 polarization in diabetic retinopathy rats

中文摘要英文摘要

目的:观察小檗碱对糖尿病视网膜病变(DR)大鼠视网膜巨噬细胞糖酵解及M2型极化的影响.方法:75只雄性SD大鼠随机分为对照组(15只)和DR组(60只).DR造模成功后,随机分为模型组、小檗碱低和高剂量组、羟苯磺酸钙组,每组15只.小檗碱低、高剂量组分别灌胃100、200 mg/kg小檗碱,羟苯磺酸钙组灌胃135 mg/kg羟苯磺酸钙,对照组与模型组灌胃生理盐水,每日1次,连续4周.伊文斯蓝染色法检测视网膜新生血管形成率;ELISA法检测血清血管内皮生长因子(VEGF)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平及视网膜组织中TNF-α、IL-6、IL-1β水平;HE染色观察视网膜组织病理学改变;TUNEL染色法检测细胞凋亡率;RT-qPCR法检测视网膜巨噬细胞中缺氧诱导因子-1α(HIF-1α)、葡萄糖转运蛋白1(GLUT1)、己糖激酶2(HK2)mRNA表达水平;West-ern blot法检测巨噬细胞中精氨酸酶-1(Arg1)、甘露糖受体(CD206)蛋白表达水平.结果:与对照组比较,模型组大鼠血清VEGF、MDA水平升高,SOD水平降低;视网膜组织呈病理损伤,新生血管形成率、TNF-α、IL-6、IL-1 β、细胞凋亡率升高;视网膜巨噬细胞中HIF-1α、GLUT1、HK2 mRNA表达水平升高,Arg1、CD206蛋白表达水平降低(P<0.05).与模型组比较,小檗碱低和高剂量组、羟苯磺酸钙组上述指标变化趋势均相反;其中小檗碱高剂量组干预效果优于低剂量组(P<0.05).结论:小檗碱可能通过抑制巨噬细胞糖酵解并促进其向M2型极化从而减轻DR大鼠视网膜炎症与血管损伤.

Aim:To observe the effects of berberine on macrophage glycolysis and M2 polarization in the retina of rats with diabetic retinopathy(DR).Methods:Seventy-five male SD rats were randomly divided into control group(15 rats)and DR group(60 rats).After successful establishment of the DR model,rats were randomly divided into model group,berberine low-and high-dose groups,and calcium dobesilate group,with 15 rats in each group.The berberine low-and high-dose groups were administered berberine by gavage at doses of 100 and 200 mg/kg,respectively.The calcium dobesilate group was administered 135 mg/kg calcium dobesilate by gavage.The control group and the model group were given normal saline by gavage.All treatments were administered once daily for 4 consecutive weeks.Retinal neovascularization rate was assessed by Evans blue staining.Serum levels of vascular endothelial growth factor(VEGF),malondialdehyde(MDA),and superox-ide dismutase(SOD),as well as TNF-α,IL-6,and IL-1β levels in retinal tissue,were measured by ELISA.Retinal his-topathological changes were observed by HE staining.The apoptosis rate was detected by TUNEL staining.The mRNA ex-pression levels of hypoxia-inducible factor-1α(HIF-1 α),glucose transporter 1(GLUT1),and hexokinase 2(HK2)in retinal macrophages were detected by RT-qPCR.The protein expression levels of arginase-1(Arg1)and mannose receptor(CD206)in macrophages were detected by Western blot.Results:Compared with control group,model group exhibited elevated serum VEGF and MDA levels,reduced SOD level,marked retinal damage,higher neovascularization rate,increased TNF-α,IL-6,IL-1β levels,and apoptosis rate,as well as up-regulated HIF-1α,GLUT1,and HK2 mRNA levels,and down-regulated Arg1 and CD206 protein levels in retinal macrophages(P<0.05).Berberine(both doses)and calcium dobesilate reversed these changes,with the berberine high-dose group showing the better effects than the low-dose group(P<0.05).Conclusion:Berberine may mitigate inflammation and vascular injury in DR by inhibiting macrophage glycolysis and promoting their po-larization towards the M2 phenotype.

张岭;姚倩;沈智远;杨琛;孙福云

沧州市中心医院肾内二科 河北沧州 061000保定市第一中心医院眼科 河北保定 071000保定市第一中心医院康复科 河北保定 071000沧州市中心医院肾内二科 河北沧州 061000沧州市中心医院肾内二科 河北沧州 061000

医药卫生

小檗碱糖尿病视网膜病变氧化应激血管损伤巨噬细胞糖酵解M2型极化大鼠

berberinediabetic retinopathyoxidative stressvascular injurymacrophage glycolysisM2 polarizationrat

《郑州大学学报(医学版)》 2026 (5)

48-53,6

河北省医学科学研究项目(20261307)

10.13705/j.issn.1671-6825.2025.10.147

评论