苯磺酸氨氯地平通过调控MAPK/ERK信号通路影响大鼠主动脉夹层血管修复的研究  

The effects of amlodipine besylate on vessel healing of aortic dissection in rats by regulating MAPK/ERK signaling pathway

作　　者：张璐 廖辉 王旭 朱夔妞 杨红霞 唐雪龙 ZHANG Lu;LIAO Hui;WANG Xu;ZHU Kuiniu;YANG Hongxia;TANG Xuelong(Biological Testing Room,Huzhou Insistute for Food and Drug Control,Huzhou 313000,China;不详)

机构地区：[1]湖州市食品药品检验研究院生物检测室,313000 [2]湖州市第一医院药剂科

出　　处：《心电与循环》2022年第4期350-354,共5页Journal of Electrocardiology and Circulation

摘　　要：目的研究苯磺酸氨氯地平对大鼠主动脉夹层血管修复的影响及其机制。方法50只SD大鼠分为模型组、低剂量组、中剂量组、高剂量组和对照组,各10只。除对照组外的4组采用羟乙基乙二胺150 mg·kg-1·d-1灌胃行主动脉夹层造模,造模成功后,低剂量组、中剂量组、高剂量组分别予0.04、0.08、0.16 mg·kg-1·d-1苯磺酸氨氯地平溶液灌胃,行HE染色观察胸主动脉结构变化,比较各组大鼠肉瘤(Ras)、快速加速纤维内瘤(Raf)、丝裂原活化蛋白激酶(MAPK)、胞外信号调节激酶(ERK)1/2、基质金属蛋白酶(MMP)-2、MMP-6、金属蛋白酶组织抑制因子(TIMP)1、TIMP2蛋白水平。结果模型组血管壁撕裂,出现双桶状的主动脉。低剂量组、中剂量组、高剂量组的主动脉血管壁撕裂程度依次降低。低剂量组、中剂量组、高剂量组、模型组的Ras、Raf、MAPK、ERK1/2、MMP-2、MMP-6蛋白表达水平均高于对照组,低剂量组、中剂量组、模型组上述指标表达水平均高于高剂量组,差异均有统计学意义(均P<0.05)。低剂量组、中剂量组、高剂量组、模型组MMP-2、MMP-6蛋白表达水平均高于对照组,TIMP1、TIMP2蛋白表达水平均低于对照组,差异均有统计学意义(均P<0.05)。结论MAPK/ERK信号通路参与羟乙基乙二胺诱导主动脉夹层的形成过程,苯磺酸氨氯地平可通过调控MAPK/ERK信号通路促进主动脉壁修复。Objective To investigate the effect of amlodipine besylate on vessel healing of aortic dissection in rats and its mechanisms.Methods Fifty SD rats were divided into model group,low-dose group,middle-dose group,high-dose group and control group with 10 rats in each group.All rat except control group were irrigated with amino ethyl ethanol amine(AEEA)150 mg·kg-1·d-1to induce aortic dissection model.After rat model was established,rats in low-dose group,middle-dose group and high-dose group were irrigated with 0.04、0.08、0.16 mg·kg-1·d-1amlodipine besylate,respectively.HE staining was used to observe structure changes of thoracic aorta.Ras,Raf,mitogen-activated protein kinase(MAPK),extracellular signal-regulated kinase(ERK)1/2,and matrix metalloproteinases(MMP)-2,MMP-6,tissue inhibitor of metalloproteinase(TIMP)1 and TIMP2 were compared between groups.Results In the model group,the vessel wall tear occurred and a double barrel aorta formed.The degree of tear decreased in turn from low-dose group,middle dose group to high dose group.The levels of Ras,Raf,MAPK,ERK1/2,MMP-2 and MMP-6 were significantly higher in low-dose group,middle-dose group,high-dose group and model group than in the control group,and higher in low-dose group,middle-dose group and model group than in high-dose group(all P<0.05).The protein expression levels of MMP-2 and MMP-6 in low-dose group,medium-dose group,high-dose group and model group were higher than those in control group,while the protein expression levels of TIMP1 and TIMP2 were lower than those in control group(all P<0.05).Conclusion The MAPK/ERK signaling pathway is involved in the formation of aortic dissection induced by AEEA.Amlodipine can improve aortic healing by regulating MAPK/ERK signaling pathway.

关 键 词：苯磺酸氨氯地平 大鼠 MAPK/ERK信号通路 羟乙基乙二胺 主动脉夹层 

分 类 号：R543.1[医药卫生—心血管疾病]