金银花水提物对小鼠糖尿病视网膜病的改善作用  

Effect of Lonicerae Japonicae Flos aqueous extract on amelioration of diabetic retinopathy

作　　者：周玲玉[1,2] 余增洋 帕丽达.阿不力孜 季莉莉[2] 

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011 [2]上海中医药大学中药研究所中药标准化教育部重点实验室中药新资源与质量标准综合评价国家中医药管理局重点研究室上海市复方中药重点实验室,上海201203

出　　处：《中国药理学通报》2015年第12期1710-1714,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81173517)

摘　　要：目的观察金银花水提物(Lonicerae Japonicae Flos aqueous extract,FL)对糖尿病视网膜病(diabetic retinopathy,DR)的改善作用及其机制。方法采用链脲佐菌素(streptozotocin,STZ)腹腔注射制备C57小鼠糖尿病模型,给药2个月后形成了DR早期病程阶段即非增殖性糖尿病视网膜(non-proliferative DR,NPDR)。使用伊文氏蓝实验检测血-视网膜屏障(blood-retinal barrier,BRB)的渗漏情况;运用Western blot实验检测相关蛋白的表达;酶联免疫实验(Enzyme-linked immunosorbent assay,ELISA)检测血清中炎性因子的表达。结果伊文氏蓝实验发现FL可以剂量依赖性的抑制STZ诱导糖尿病小鼠中发生的BRB渗漏。Western blot结果显示FL可以抑制STZ诱导糖尿病小鼠视网膜组织中核因子κB(nuclear factor-κB,NF-κB)p65亚单位的转核激活,FL还可以抑制视网膜组织中kappa B抑制剂(inhibitor ofκB,IκB)、抑制性κB激酶(inhibitor of nuclear factorκB kinase,IKK)、p65的磷酸化激活。进一步研究发现FL可以抑制STZ诱导糖尿病小鼠视网膜组织中升高的小胶质细胞/巨噬细胞特异性蛋白(ionized calcium binding adapter molecule 1,Iba1)的表达,提示FL可以抑制神经小胶质细胞的活化。ELISA实验结果发现FL能降低STZ诱导糖尿病小鼠血清中升高的炎性细胞因子如白介素(interleukin,IL)-6,-1β。结论 FL可能通过抑制神经小胶质细胞的活化,抑制NF-κB介导的炎性信号通路,缓解视网膜的炎性损伤和BRB的渗漏,从而发挥改善DR的药效活性。Aim To observe the effect of Lonicerae Japonicae Flos aqueous( FL) on the amelioration of diabetic retinopathy( DR) and its engaged mechanism induced by FL. Methods Streptozotocin( STZ)-induced diabetes in C57 mice was used. Two months after STZ injection,non-proliferative DR( NPDR) was developed in mice,which is the early stage of DR. Evans Blue assay was used to detect the leakage of bloodretinal barrier( BRB). Western blot analysis was used to detect the expression of proteins. Enzyme-linked immunosorbent assay( ELISA) was used to detect the contents of serum inflammatory cytokines. Results The results of Evans Blue Assay showed FL inhibited the leakage of BRB in STZ-induced diabetic mice in a dose-dependent manner. Western blot results showed that FL inhibited the transcriptional activation of p65 subunit of nuclear factor κB( NF-κB),and reduced the phosphorylated activation of inhibitor of κB( IκB),inhibitor of nuclear factor κB kinase( IKK),and p65 in retinas in STZ-induced diabetic mice. Furthermore,FL reduced the elevated expression of ionized calcium binding adapter molecule 1( Iba1) in retinas from STZ-induced diabetic mice,which indicated the inhibition on microglia cells was induced by FL. ELISA results demonstrated that FL reduced the increased serum contents of some inflammatory cytokines including interleukin( IL)-6,-1β. Conclusion FL ameliorates DR by attenuating retinal inflammation and BRB leakage via inhibiting the activation of microglia cells and abrogating NF-κB-mediated inflammatory signaling pathway.

关 键 词：糖尿病视网膜病 金银花 血-视网膜屏障 炎性损伤 NF-ΚB Iba1 

分 类 号：R-332[医药卫生] R284.1