Protective effects of piperine on the retina of mice with streptozotocin-induced diabetes by suppressing HIF-1/VEGFA pathway and promoting PEDF expression  

作　　者：Pu Zhang Yan-Dan Zhou Yao Tan Ling Gao 

机构地区：[1]Department of Ophthalmology,the Second Xiangya Hospital,Central South University,Changsha 410011,Hunan Province,China [2]Changsha Aier Eye Hospital,Changsha 410015,Hunan Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2021年第5期656-665,共10页国际眼科杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China(No.81072221);Projects of Research and Development in Key Areas of Hunan Province(No.2017SK2020;No.2020SK2133);the Natural Science Foundation of Hunan Province(No.2020JJ5005)。

摘　　要：AIM:To evaluate the protective mechanisms of piperine in the retina of mice with streptozotocin-induced diabetes.METHODS:In experiments in vitro,stimulation by chemical hypoxia was established in ARPE-19 cells.Then,the expression of hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor A(VEGFA),and pigment epithelium-derived factor(PEDF)was assessed at the m RNA and protein levels.In experiments in vivo,diabetes mellitus was established by intraperitoneally injecting 150 mg/kg streptozotocin once.After 3 wk of the onset of diabetes,15 mg/kg piperine was intraperitoneally injected once daily for 1 or 3 wk.Then,the retinal morphology and m RNA and protein expression were assessed.RESULTS:In hypoxia,1-100μmol/L piperine significantly decreased the expression of VEGFA m RNA and increased the expression of PEDF m RNA without affecting HIF-1αm RNA.Meanwhile,100μmol/L piperine substantially decreased the protein level of VEGFA and increased the protein level of PEDF.The HIF-1αprotein level was also hampered by piperine.In the diabetic retina of mice,the morphological damage was alleviated by piperine.Likewise,the retinal vascular leakage was substantially decreased by piperine.Further,the protein levels of HIF-1αand VEGFA were significantly reduced by piperine.Moreover,the level of the antiangiogenic factor of PEDF dramatically increased by piperine.CONCLUSION:Piperine may exert protective effects on the retina of mice with diabetes via regulating the pro-antiangiogenic homeostasis composed of HIF-1/VEGFA and PEDF.

关 键 词：diabetes diabetic retinopathy hypoxiainducible factor-1α/vascular endothelial growth factor A pathway pigment epithelium-derived factor PIPERINE MICE 

分 类 号：R285.5[医药卫生—中药学]