摘要
目的探讨熊去氧胆酸(UDCA)对动脉血管内膜增生的影响及其机制。方法选择人脐静脉细胞融合细胞EA.hy926,体外检测UDCA对白细胞介素-8(IL-8)诱导的血管生成的影响。选择BALB/cA雄性小鼠60只,分为对照组、模型组及实验组。对照组皮下接种基质胶、内皮细胞;模型组皮下接种基质胶、内皮细胞及IL-8混合液;实验组皮下接种基质胶、内皮细胞、IL-8及UDCA的混合液。以血红蛋白检测试剂盒检测基质胶中血红蛋白的浓度,以苏木精-伊红(HE)染色观察各组小鼠基质胶团块,以蛋白质印迹法检测IL-8、低氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)蛋白表达。结果模型组、对照组和UDCA组细胞血管季节数量分别为(469.52±56.34),(400.16±52.16),(426.39±42.16)个,血管长度分别为(3856.24±264.28),(2156.56±158.62),(2987.64±185.24)μm,血管面积分别为(3956.21±241.37),(2563.15±246.31),(2985.34±256.14)μm^(2),血红蛋白浓度分别为(162.34±30.45),(116.35±26.51),(132.61±25.34)g·L^(-1),模型组与对照组和UDCA组比较,差异均有统计学意义(均P<0.05)。HE染色发现,模型组小鼠基质胶团块血管数量明显高于对照组,而实验组小鼠基质胶团块血管数量明显低于模型组(P<0.05)。模型组小鼠HIF-1α/IL-8/VEGF蛋白表达水平明显高于对照组,实验组小鼠HIF-1α/IL-8/VEGF蛋白表达水平明显低于模型组(均P<0.05)。结论UDCA可抑制体内、体外动脉血管内膜的增生,其机制可能与调控HIF-1α/IL-8/VEGF相关通路相关蛋白有关。
Objective To study the effect of ursodeoxycholic acid on intimal hyperplasia of artery and its mechanism.Methods The human umbilical vein cell fusion cell EA.hy926 was selected to detect the effect of ursodeoxycholic acid on interleukin-8(IL-8)induced angiogenesis in vitro.Sixty BALB/cA male mice were selected and divided into control group,model group and experimental group.Control group was subcutaneously inoculated with matrix glue and endothelial cells;model group was subcutaneously inoculated with the matrix glue,endothelial cells and IL-8 mixture;experimental group was subcutaneously inoculated with the mixture of matrix glue,endothelial cells,IL-8 and ursodeoxycholic acid.The hemoglobin concentration in matrix gum was detected by hemoglobin detection kit.Matrix micelles were observed by hematoxylin-eosin(HE)staining,and the protein expressions of IL-8 hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Westernblot.Results The seasonal number of blood vessels in model group,control group and UDCA group were(469.52±56.34),(400.16±52.16),(426.39±42.16),the length of blood vessels were(3856.24±264.28),(2156.56±158.62),(2987.64±185.24)μm,vascular area were(3956.21±241.37),(2563.15±246.31),(2985.34±256.14)μm^(2),hemoglobin concentration were(162.34±30.45),(116.35±26.51),(132.61±25.34)g·L^(-1),the difference between model group,control group and UDCA group were statisticallysignificant(allP<0.05).HE staining showed that the number of matrix micelles in model group was significantlyhigher than that of control group,while that of experimental group was significantly lower than that in model group(P<0.05).The expression level of HIF-1α/IL-8/VEGF protein in model group was significantly higher than thatin control group,and the expression level of HIF-1α/IL-8/VEGF protein in experimental group was significantlylower than that in model group(allP<0.05).Conclusion Ursodeoxycholic acid can inhibit intima hyperplasiain vivoandin vitro,and the mechanism may be related to the regulation of HIF-1α/IL-8/VEGF-related pathway-related proteins.
作者
曾光
金永志
黄毅
李梦帆
黄荣
ZENG Guang;JIN Yong-zhi;HUANG Yi;LI Meng-fan;HUANG Rong(Department of Vascular Surgery,Putuo District Central Hospital,Shanghai,Shanghai 200062,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第21期2550-2553,共4页
The Chinese Journal of Clinical Pharmacology
基金
上海市普陀区特色专病建设基金资助项目(2020tszb01)。
