脂肪细胞型脂肪酸结合蛋白(adipocyte fatty-acid binding protein A-FABP,FABP4,或ap2),属于运输长链脂肪酸的低分子量胞浆蛋白家族成员.近年来研究发现ap2的表达量与动脉粥样硬化的发生和发展有十分密切的关系,ap2为靶点的治疗方法成为治疗动脉粥样硬化等相关疾病的焦点.为此采用ERK1/2抑制剂PD98059和UO126处理小鼠单核巨噬细胞RAW264.7和腹膜巨噬细胞,ap2的表达被明显的抑制,并呈现一定的时间和浓度依赖性.因而ERK1/2抑制剂可能对动脉粥样硬化有一定的治疗作用.
Clinical observations indicate that DanHong Injection(DHI)can increase blood flow and reduce various syndromes in patients with cardiovascular disease.However,it still needs to define the function of DHI and the involved mechanisms in details,such as the protective effect on the development of primary abdominal aortic aneurysms(AAAs).In this study,we determined whether DHI is able to inhibit AAA in apoE knockout(apoE-/-)mice.Thirty apoE-/-male mice on high-fat diet(0.5%cholesterol,21%fat)were randomly divided into two groups and received i.p.injection of saline(100 lL/day)and DHI(100 lL/day),respectively,for 16 weeks.At the end of experiment,we determined the development of atherosclerosis in en face aorta and aneurysms,pathological morphology of arterial wall,and serum lipid levels.We also determined the expression of monocyte chemoattractant protein-1(MCP-1),MMP-2,and MMP-9mRNA in aortic wall using real-time RT-PCR.Our results indicated that high-fat diet induced the development of AAAs in apoE-/-mice,but the induction was totally blocked by DHI(P\0.01).The result of staining of abdominal aortic cross sections showed that DHI maintained the collagen content in arterial wall,thereby preventing the animals from the development of AAA.Although DHI had little effect on serum total-and LDLcholesterol levels,it reduced the expression of MCP-1,MMP-2,and MMP-9 mRNA in aortic wall(P\0.01).Taken together,our study suggests that DHI can inhibit the high-fat diet-induced AAA formation.The inhibitory effects may be related to the maintenance of the collagen content and inhibition of expression of AAA-related genes.Our study may suggest a new application of DHI in clinics.
