阿托伐他汀对氧化型低密度脂蛋白诱导内皮细胞损伤的保护作用  

Protective effect of atorvastatin on the endothelial cells injury induced by oxidized low-density lipoprotein

作　　者：李霞[1] 邸亚丽[1] 亢小丽[1] 李昌义[1] 孙淑娴[1] 杨立明[1] 张宇[1] 纪征[1] LI Xia;DI Ya-li;KANG Xiao-li;LI Chang-yi;SUN Shu-xian;YANG Li-ming;ZHANG Yu;JI Zheng(Department One of Cardiology,Tangshan Gongren Hospital,Tangshan 063000,Hebei Province,China)

机构地区：[1]唐山工人医院心内一科,河北唐山063000

出　　处：《中国临床药理学杂志》2021年第10期1184-1188,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河北省重点研发计划基金资助项目(16277736D)。

摘　　要：目的基于Ras同源基因家族蛋白A(RhoA)/Rho相关卷曲螺旋蛋白激酶(ROCK)信号通路研究阿托伐他汀对氧化型低密度脂蛋白(ox-LDL)诱导内皮细胞损伤的保护作用。方法用ox-LDL构建HUVEC细胞损伤模型,并将模型细胞分为模型组、对照组和实验组,另取正常细胞作为空白组。空白组和模型组均在培养基中加入等量的0.9%NaCl进行培养;对照组在培养基中加入10μmol·L^(-1) Y-27632 5μL进行培养;实验组在培养基中加入10μmol·L^(-1)阿托伐他汀5μL进行培养。用噻唑蓝法检测细胞活力的变化,用流式细胞术检测细胞凋亡的变化,用蛋白质印迹法检测磷酸化RhoA(p-RhoA)、ROCK1和ROCK2蛋白的表达水平。结果实验组、对照组、模型组和空白组的细胞相对活力分别为0.78±0.08,0.75±0.11,0.43±0.06和1.01±0.02,细胞凋亡率分别为(38.78±0.76)%,(38.56±0.95)%,(69.55±0.36)%和(9.85±0.26)%,p-RhoA相对表达量分别为2.13±0.05,2.15±0.03,4.32±0.05和0.99±0.01,ROCK1相对表达量分别为2.88±0.02,2.86±0.04,4.71±0.06和0.97±0.04,ROCK2相对表达量分别为2.25±0.03,2.21±0.07,4.46±0.02和1.01±0.02。模型组的上述指标与实验组、对照组和空白组比较,差异均有统计意义(均P<0.05)。结论阿托伐他汀对ox-LDL诱导内皮细胞损伤具有保护作用,其作用机制可能与抑制RhoA/Rho信号通路有关。Objective To investigate the mechanism of atorvastatin promoting endothelial cell from damage induced by oxidized low-density lipoprotein(ox-LDL) based on ras homolog gene family member A(RhoA)/Rho-associated coiled-coil-containing protein kinase(Rho) signaling pathway. Methods ox-LDL was used to construct HUVEC cell injury model. the model cells were divided into model group, control group and experimental group, and normal cells were taken as the blank group. Both the blank group and the model group were cultured with the same amount of 0.9% NaCl in the culture medium;the control group was cultured with 10 μmol·L^(-1) ROCK inhibitor(Y-27632) 5 μL in the culture medium;the experimental group was cultured with 10 μmol ·L^(-1) atorvastatin 5 μL in the culture medium. The thiazole blue method was used to detect the changes in cell viability flow cytometry was used to detect the changes in cell apoptosis,and Western blot was used to detect the expression levels of phosphorylated RhoA( p-RhoA),ROCK1 and ROCK2 proteins. Results The relative viability of cells in the experimental group,control group and model group,blank group were 0. 78 ± 0. 08,0. 75 ± 0. 11,0. 43 ± 0. 06 and1. 01 ± 0. 02,the cell apoptosis rates were( 38. 78 ± 0. 76) %,( 38. 56 ± 0. 95) %,( 69. 55 ± 0. 36) % and( 9. 85 ± 0. 26) %,the relative expressions of p-RhoA were 2. 13 ± 0. 05,2. 15 ± 0. 03,4. 32 ± 0. 05 and0. 99 ± 0. 01,the relative expressions of ROCK1 were 2. 88 ± 0. 02,2. 86 ± 0. 04,4. 71 ± 0. 06 and 0. 97 ± 0. 04,the relative expressions of ROCK2 were 2. 25 ± 0. 03,2. 21 ± 0. 07,4. 46 ± 0. 02 and 1. 01 ± 0. 02. The differences of the above indicators between the model group and the experimental group,control group,blank group,were statistically significant( all P < 0. 05). Conclusion Atorvastatin can protect against endothelial cell injury induced by ox-LDL,and its mechanism may be related to the inhibition of RhoA/Rho signaling pathway.

关 键 词：阿托伐他汀 氧化型低密度脂蛋白 内皮损伤 Ras同源基因家族蛋白A/Rho相关卷曲螺旋蛋白激酶信号通路 

分 类 号：R972.6[医药卫生—药品]