血小板微粒介导miR-4306调控糖尿病大鼠主动脉血管内皮细胞损伤的作用及机制研究  

Effects and mechanisms of miR-4306,mediated by platelet microparticles,on vascular endothelial cell injury in the aorta of diabetic rats

作　　者：王瑞青[1] 郑彩虹 朱巍[1] 郭彩红[1] WANG Ruiqing;ZHENG Caihong;ZHU Wei;GUO Caihong(Department of Endocrinology,Beijing Aerospace General Hospital,Beijing 100076,China;Department of Endocrinology,Shanxi Bethune Hospital,Taiyuan 03000)

机构地区：[1]北京航天总医院内分泌科,北京100076 [2]山西白求恩医院内分泌科,太原030000

出　　处：《中国比较医学杂志》2021年第9期105-112,共8页Chinese Journal of Comparative Medicine

摘　　要：目的探讨分析糖尿病大鼠血小板微颗粒(platelet microparticles,PMPs)在主动脉血管内皮损伤的作用及机制。方法将SD大鼠随机分为对照组(NC组)和糖尿病组(DM组),分离纯化血小板微颗粒,原代培养内皮细胞,免疫荧光激光共聚焦检测内皮型一氧化氮合酶、半胱氨酸蛋白酶3(Caspase-3),流式细胞术检测内皮细胞凋亡情况,qRT-PCR检测miR-4306表达,蛋白免疫印迹法检测VEGFA/ERK1/2/NF-κB信号通路相关蛋白。结果DM组eNOS、Caspase-3阳性表达率及细胞凋亡率,与NC组比较差异有统计学意义(P<0.05或P<0.01)。mimic-M组、inhibitor-M组miR-4306相对表达量与miR-M组比较,差异有统计学意义(t=3.821、4.597,P<0.05或P<0.01)。mimic-M组miR-4306相对表达量与inhibitor-M组比较,差异有统计学意义(P<0.01)。M组miR-4306相对表达量与Ctrl组比较,差异有统计学意义(P<0.01)。mimic-M组、inhibitor-M组VEGFA、NF-κBp65、p-IκBα及p-ERK相对表达量与M组比较,差异有统计学意义(P<0.05或P<0.01),M组VEGFA、NF-κBp65、p-IκBα及p-ERK相对表达量与Ctrl组比较,差异有统计学意义(P<0.05或P<0.01)。结论糖尿病大鼠分泌PMPs导致主动脉血管内皮细胞损伤,其作用机制可能与激活miR-4306/VEGFA/ERK1/2/NF-κB信号通路有关。Objective To investigate the role and mechanisms of platelet microparticles( PMP) sin vascular endothelial injury of the diabetic aorta. Methods SD rats were randomly divided into the normal( NC) and diabetic( DM) groups. PMPs were isolated and purified. Next,primary cultured endothelial cells were transfected with microRNA( miR)-4306 to detect PMPs in vascular endothelial cells. The effects of activity and the effects on the miR-4306/vascular endothelial growth factor A( VEGFA)/extracellular signal-regulated kinase( ERK) 1/2/nuclear factor κB( NF-κB)signaling pathway were evaluated. Results The positive expression and apoptosis rates of endothelial nitric oxide synthase( eNOS) and caspase-3 in the DM group were significantly different from those in the NC group( P<0. 05 or P<0. 01). The relative expression of miR-4306 in the mimic-M group and inhibitor-M group was significantly different from that in the miR-M group( t = 3. 821,4. 597,P< 0. 05 or P< 0. 01). Moreover,the relative expression of miR-4306 in the mimic-M group was significantly different from that in the inhibitor-M group( P< 0. 01). The relative expression of miR-4306 in M group was significantly different from that in Ctrl group( P< 0. 01). In addition,the relative expression of VEGFA,NF-κBp65,p-IκBα and p-ERK in the mimic-M group and inhibitor-M group was significantly different from that in M group( P<0. 05 or P<0. 01). The relative expression of VEGFA,NF-κBp65,p-IκBα and p-ERK in the M group was significantly different from that of Crtl group( P<0. 05 or P<0. 01). Conclusions PMPs may cause endothelial damage in the diabetic aorta,the underlying mechanism may be related to the activation of miR-4306/VEGFA/ERK1/2/NF-κB signaling.

关 键 词：糖尿病 动脉粥样硬化 血小板微颗粒 血管内皮细胞 miR-4306 

分 类 号：R-33[医药卫生]