摘要
目的探讨瑞舒伐他汀对高同型半胱氨酸(Hcy)诱导小鼠动脉粥样硬化形成的影响及其机制。方法 46只小鼠分为五组:A组采用普通饲料喂养,B组采用高蛋氨酸喂养小鼠构建高Hcy模型,C组采用高蛋氨酸喂养同时用叶酸0.8mg/kg灌胃,D组采用高蛋氨酸喂养同时用瑞舒伐他汀0.8mg/kg灌胃,E组采用高蛋氨酸喂养同时用瑞舒伐他汀1.6mg/kg灌胃。小鼠经眼静脉采血,检测各组Hcy含量。留取小鼠主动脉标本,HE染色并用图像分析测定主动脉斑块的相对面积。培养小鼠单核细胞系,分别采用Hcy、Hcy+蛋白激酶B(Akt)抑制剂MK-2206、Hcy+瑞舒伐他汀处理细胞后,Western blot检测磷酸化Akt(p-Akt)、Akt、MMP-9的表达。结果 A、E组小鼠无动脉斑块形成。B、C、D组分别有2、1、1只小鼠形成动脉粥样硬化斑块,斑块面积/血管腔面积比例分别为56.38%、20.92%、18.30%,C、D组较B组小(P<0.05);C、D、E组Hcy低于B组(P<0.05)。在Hcy诱导小鼠单核细胞实验中,小鼠单核细胞随着Hcy处理时间的延长,MMP-9的表达及p-Akt水平逐步增强(P<0.01)。用Akt抑制剂抑制其磷酸化后,Hcy不能诱导MMP-9的上调;用瑞舒伐他汀处理细胞后能抑制由Hcy诱导的Akt磷酸化(P<0.01),致MMP-9的表达下调(P<0.05)。结论瑞舒伐他汀可以通过抑制Hcy诱导的Akt磷酸化来抑制小鼠动脉粥样硬化斑块的形成。
Objective To study the impact and underlying mechanism of rosuvastatin on atherosclerosis formation induced by high homocysteine in mice.Methods Mouse model with high homocysteine（Hcy）was established by high methionine feeding（Group B）.In addition to methionine feeding,group C was gavaged with folic acid,group D was gavaged with rosuvastatin 0.8 mg/kg and group E was gavaged with rosuvastatin 1.6 mg/kg.Group A was given normal diet.After intervented with folic acid or different concentrations of rosuvastatin,blood sample from ophthalmic vein was collected for detecting the contents of Hcy.HE staining of mouse aorta was performed and the relative area of aortic plaque was determined by image analysis.The mouse mononuclear cell line J774 A.1 was cultured and then was treated with Hcy,Hcy＋ MK-2206（Akt inhibitor）,Hcy＋ rosuvastatin,respectively.The expressions of p-Akt,Akt and MMP-9 were detected by Western blot.Results The mice in group A and group E had no arterial plaque formation.The arterial plaque was seen in two mice of group B,one mouse of group C and one mouse of group D with the area ratio of plaque to vasculature of 56.38%,20.92% and 18.30%,respectively（P〈0.05）.The Hcy level in groups of C,D and E was significantly lower than that in group B（P〈0.05）.In the Hcy-induced mouse mononuclear cells,the expressions of MMP-9 and the phosphorylation of Akt increased gradually as Hcy treatment was prolonged.The Hcy treatment did not induce the upregulation of MMP-9 after the inhibition of phosphorylation by Akt inhibitors.The expression of MMP-9 was down-regulated by Hcy-induced Akt phosphorylation after treated with rosuvastatin.Conclusion Rosuvastatin can inhibit the formation of atherosclerosis by inhibiting Hcy-induced Akt phosphorylation in mice.
作者
刘爱宁
杨文刚
鞠树红
聂丹凤
孙一鸣
马骏
周晖
LIU Aining, YANG Wengang, JU Shuhong, et al(Deparment of Neurology, Liqun Hospital of Putuo District, Shanghai 200333, CHIN)
出处
《江苏医药》
CAS
2018年第3期239-242,I0002,共5页
Jiangsu Medical Journal
基金
上海市卫生计生委科研课题面上项目(201540186)
