中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2014年
4期
340-344
,共5页
秦秀虹%张珍珍%许海涛%张丽红%吴雅臻
秦秀虹%張珍珍%許海濤%張麗紅%吳雅臻
진수홍%장진진%허해도%장려홍%오아진
Notch1%糖尿病视网膜病变%视网膜%血管内皮细胞%多聚二磷酸腺苷核糖聚合酶-1
Notch1%糖尿病視網膜病變%視網膜%血管內皮細胞%多聚二燐痠腺苷覈糖聚閤酶-1
Notch1%당뇨병시망막병변%시망막%혈관내피세포%다취이린산선감핵당취합매-1
Notch1%Diabetic retinopathy%Retina%Vascular endothelial cell%Poly(adenosine diphosphate-ribose) polymerase 1
背景 多聚二磷酸腺苷核糖聚合酶-1(PARP-1)在糖尿病视网膜病变(DR)发生过程中具有重要作用,而Notch1是生物体重要的信号转导通路,可能参与对视网膜新生血管性疾病的拮抗过程,Notch1是否参与了DR的发生还未得到证实. 目的 探讨Notch1、Dll4、PARP-1、Akt、核因子-κB(NF-κB)及caspase-3在糖尿病小鼠视网膜组织及高糖视网膜血管内皮细胞(RVECs)中的表达. 方法 建立糖尿病小鼠模型,应用免疫组织化学法和Western blot法检测Notch1、Dll4、PARP-1、Akt、NF-κB及caspase-3在糖尿病小鼠视网膜组织及RVECs的表达.结果 Notch1、Dll4、p-Akt在糖尿病小鼠视网膜组织中的表达量比正常对照组明显降低,而PARP-1、caspase-3在糖尿病小鼠视网膜组织中的表达量比正常对照组明显增加,差异均有统计学意义(均P<0.05),但NF-κB的表达量无明显变化,差异无统计学意义(t=0.748,P=0.530).RVECs中Notch1、p-Akt的表达量随葡萄糖浓度的增高而增加,而剪切型PARP-1、caspase-3的表达量则随葡萄糖浓度的增高而降低,在葡萄糖浓度为30 mmol/L时上述变化最显著,与正常对照组比较差异均有统计学意义(均P<0.05),而NF-κB的表达量无明显变化. 结论 在糖尿病小鼠视网膜中,剪切型PARP和caspase-3蛋白的表达上调,但Notch1、p-Akt蛋白的表达量下调.剪切型PARP和caspase-3表达量随葡萄糖浓度的增高而增加,Notch1、p-Akt则相反.
揹景 多聚二燐痠腺苷覈糖聚閤酶-1(PARP-1)在糖尿病視網膜病變(DR)髮生過程中具有重要作用,而Notch1是生物體重要的信號轉導通路,可能參與對視網膜新生血管性疾病的拮抗過程,Notch1是否參與瞭DR的髮生還未得到證實. 目的 探討Notch1、Dll4、PARP-1、Akt、覈因子-κB(NF-κB)及caspase-3在糖尿病小鼠視網膜組織及高糖視網膜血管內皮細胞(RVECs)中的錶達. 方法 建立糖尿病小鼠模型,應用免疫組織化學法和Western blot法檢測Notch1、Dll4、PARP-1、Akt、NF-κB及caspase-3在糖尿病小鼠視網膜組織及RVECs的錶達.結果 Notch1、Dll4、p-Akt在糖尿病小鼠視網膜組織中的錶達量比正常對照組明顯降低,而PARP-1、caspase-3在糖尿病小鼠視網膜組織中的錶達量比正常對照組明顯增加,差異均有統計學意義(均P<0.05),但NF-κB的錶達量無明顯變化,差異無統計學意義(t=0.748,P=0.530).RVECs中Notch1、p-Akt的錶達量隨葡萄糖濃度的增高而增加,而剪切型PARP-1、caspase-3的錶達量則隨葡萄糖濃度的增高而降低,在葡萄糖濃度為30 mmol/L時上述變化最顯著,與正常對照組比較差異均有統計學意義(均P<0.05),而NF-κB的錶達量無明顯變化. 結論 在糖尿病小鼠視網膜中,剪切型PARP和caspase-3蛋白的錶達上調,但Notch1、p-Akt蛋白的錶達量下調.剪切型PARP和caspase-3錶達量隨葡萄糖濃度的增高而增加,Notch1、p-Akt則相反.
배경 다취이린산선감핵당취합매-1(PARP-1)재당뇨병시망막병변(DR)발생과정중구유중요작용,이Notch1시생물체중요적신호전도통로,가능삼여대시망막신생혈관성질병적길항과정,Notch1시부삼여료DR적발생환미득도증실. 목적 탐토Notch1、Dll4、PARP-1、Akt、핵인자-κB(NF-κB)급caspase-3재당뇨병소서시망막조직급고당시망막혈관내피세포(RVECs)중적표체. 방법 건립당뇨병소서모형,응용면역조직화학법화Western blot법검측Notch1、Dll4、PARP-1、Akt、NF-κB급caspase-3재당뇨병소서시망막조직급RVECs적표체.결과 Notch1、Dll4、p-Akt재당뇨병소서시망막조직중적표체량비정상대조조명현강저,이PARP-1、caspase-3재당뇨병소서시망막조직중적표체량비정상대조조명현증가,차이균유통계학의의(균P<0.05),단NF-κB적표체량무명현변화,차이무통계학의의(t=0.748,P=0.530).RVECs중Notch1、p-Akt적표체량수포도당농도적증고이증가,이전절형PARP-1、caspase-3적표체량칙수포도당농도적증고이강저,재포도당농도위30 mmol/L시상술변화최현저,여정상대조조비교차이균유통계학의의(균P<0.05),이NF-κB적표체량무명현변화. 결론 재당뇨병소서시망막중,전절형PARP화caspase-3단백적표체상조,단Notch1、p-Akt단백적표체량하조.전절형PARP화caspase-3표체량수포도당농도적증고이증가,Notch1、p-Akt칙상반.
Background Poly(adenosine diphosphate-ribose) polymerase 1 (PARP-1) plays an important role in the pathogenesis of diabetic retinopathy (DR),and Notch1 signal pathway is one of the important signal transduction pathways in the organism which may antagonize retinal vascular diseases.However,if Notch1 signaling pathway is involved in pathogenesis of DR has not been confirmed yet.Objective This study was to investigate the expressions of Notch1,Dll4,PARP-1,Akt,nuclear factor-κB (NF-κB) and caspase-3 in the retina of diabetic mouse model and retinal vascular endothelial cells (RVECs) under the high glucose.Methods The expressions of Notch1,Dll4,PARP-1,Akt,NF-κB and caspase-3 in the retina of diabetic mouse models were investigated using immunochemistry and Western blot method after the diabetic mouse models were established.And these proteins were detected in retinal RVECs under the high glucose by Western blot.Results The expressions of Notch1,Dll4 and phosphorylated Akt (p-Akt) in retinas reduced significantly and simultaneously companied with increases of PARP-1 and caspase-3 in diabetic mice compared with normal mice (all at P<0.05).However,no obvious change was found in the expression of NF-κB (P>0.05).Expressions of Notch1 and p-Akt in RVECs increased with the increase of glucose concentration,but expressions of cleaved PARP-1 and caspase-3 decreased,especially in the 30 mmol/L group,showing significant differences in comparison with the normal control group (all at P<0.05).But no altering of NF-κB expression was seen in the mice with diabetes mellitus.Conclusions The expressions of cleaved-PARP-1 and caspase-3 in the retinas is up-regulated,but the expressions of Notch1 and p-Akt are down-regulated in diabetic mice.