摘要
目的:研究重组人脑钠肽(rhBNP)对高糖环境下人脐静脉内皮细胞(HUVECs)的作用和机制。方法:利用高糖诱导HUVECs凋亡模型,给予rhBNP、rhBNP+自噬抑制剂3-甲基腺嘌呤(3-MA)或rhBNP+ERK通路抑制剂U0126干预,观察rhBNP对高糖诱导下HUVECs自噬、凋亡及其相关信号通路的影响。结果:体外高糖诱导HUVECs,细胞活力被抑制,细胞凋亡增加,自噬相关蛋白beclin-1表达水平和LC3-Ⅱ/LC3-Ⅰ比值均显著降低,ERK信号通路活性显著减弱(P<0.05或P<0.01)。1 mg/L rhBNP干预后细胞活力和迁移能力显著增强(P<0.01),LC3-Ⅱ/LC3-Ⅰ比值提高(P<0.05),beclin-1表达增加(P<0.01),Bax/Bcl-2比值和cleaved caspase-3蛋白水平降低,ERK蛋白水平增加(P<0.05)。加入ERK抑制剂后,beclin-1自噬蛋白表达减弱(P<0.05),提示rhBNP可能通过激活ERK信号通路促进自噬蛋白表达进而调节HUVECs的生物学活性。结论:高糖抑制ERK信号通路,自噬降低,凋亡增加;rhBNP通过激活ERK信号通路,促进自噬发生,减少细胞凋亡,保护细胞。
AIM:To investigate the effects of recombinant human brain natriuretic peptide(rhBNP)on human umbilical vein endothelial cells(HUVECs)in high glucose environment.METHODS:The apoptosis of HUVECs was induced by high concentration of glucose.The HUVECs were treated with rhBNP,rhBNP+autophagy inhibitor 3-methyl adenine(3-MA)or rhBNP+ERK inhibitor U0126,in order to investigate the effect of rhBNP on autophagy,apoptosis and related signaling pathways in the HUVECs induced by high glucose.RESULTS:The HUVECs were induced by high glucose in vitro,and the viability of HUVECs was inhibited.The apoptosis was increased,the protein levels of autophagy-related molecules beclin-1 and LC3-Ⅱ/LC3-Ⅰ were decreased,and the activity of ERK signaling pathway was decreased(P<0.05 or P<0.01).After intervention with rhBNP at 1 mg/L,the viability and migration ability of HUVECs were significantly enhanced,LC3-Ⅱ/LC3-Ⅰ level and the expression of beclin-1 were increased(P<0.05 or P<0.01),the protein levels of Bax/Bcl-2 and cleaved caspase-3 were decreased(P<0.05),and ERK protein was increased(P<0.05).After the addition of ERK inhibitor,the protein expression of beclin-1 was decreased(P<0.05),suggesting that rhBNP may promote the expression of autophagy protein by activating ERK signaling pathway,and then regulated the biological activity of HUVECs.CONCLUSION:The exposure of HUVECs to high concentration of glucose inhibits the autophagy and promotes the apoptosis by inhibiting ERK signaling pathway.The protect mechanism of rhBNP may be related to the stimulation of ERK signaling pathway to increase autophagy and reduce apoptosis.
作者
金启辉
夏江柳
鲁闻燕
有传刚
韩春茂
JIN Qi-hui;XIA Jiang-liu;LU Wen-yan;YOU Chuan-gang;HAN Chun-mao(Department of Geriatrics,Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,China;Department of Burns and Wound Repair,Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310009,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2021年第9期1612-1619,共8页
Chinese Journal of Pathophysiology
基金
浙江省中医药科技计划项目(No.2017ZA087)。
关键词
重组人脑钠肽
高糖
人脐静脉内皮细胞
细胞凋亡
自噬
Recombinant human brain natriuretic peptide
High glucose
Human umbilical vein endothelial cells
Apoptosis
Autophagy
