免疫球蛋白Fc区介导抑制脂蛋白E基因敲除鼠动脉粥样硬化形成  

The Fc region of immunoglobulin suppresses atherosclerosis in apolipoprotein E knockout mice

作　　者：袁祖贻[1] 刘艳[1] 岸本千晴[2] 盐路圭介[2] 横出正之[3] 刘治全[1] 

机构地区：[1]西安交通大学第一医院心内科,710061 [2]日本京都大学附属病院循环科 [3]日本京都大学附属病院加龄医学科

出　　处：《中华医学杂志》2003年第6期489-493,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目 ( 30 170 371)

摘　　要：目的　探讨免疫球蛋白治疗对实验性动脉粥样硬化形成的抑制作用 ,及其作用机制。方法　 6周龄的脂蛋白基因敲除鼠 (apoEKnockout,apoE-/ -)高脂餐喂养 8周或 16周 ,分别诱导早期脂质条纹和进展的复合粥样斑块形成。同时腹腔注射 1g·kg-1·d-1的人类免疫球蛋白 (IG)或免疫球蛋白Fab片段 (F(ab′) 2 ) 8周或 16周 ,观察其对早期脂质条纹形成和进展粥样斑块的抑制作用。离体实验检测IG对单核 /巨噬细胞株U937细胞表面Fc受体表达的影响。结果　与对照组相比 ,IG治疗显著降低脂质条纹面积 ( 4 2 %± 2 0 %vs 13 6 %± 4 8%,P <0 0 1)和进展复合斑块面积 ( 8 1%± 2 7%vs2 1 5 %± 3 9%,P <0 0 1) ;而F(ab′) 2 片段治疗组血管病灶面积无明显降低 (脂质条纹面积12 1%± 3 7%;粥样斑块面积 2 0 6 %± 4 8%) ,与对照组相比均P >0 0 5。免疫组化显示 ,IG治疗减少斑块内巨噬细胞浸润 ,而CD+4 、CD+8T淋巴细胞和I Ab +浸润细胞百分数无明显变化。血清脂质谱也无明显差异。离体实验表明 ,IG抑制细菌脂多糖 (LPS)诱导的单核 /巨噬细胞表面FcγⅡ受体表达。结论　IG治疗显著抑制动脉粥样硬化形成 ,其机制与抑制Fcγ受体介导的炎症作用有关。Objective To investigate the role of immunoglobulin in inhibition of atherosclerosis and its mechanism.Methods Apolipoprotein E knockout mice aged 6 weeks were fed with high fat diet containing 20% fat and 0.3% cholesterol for 8～16 weeks to induce the formation of fatty streak and fibrofatty plaque and were injected intraperitoneally with either human intact immunoglobulin (1 g·kg -1 ·d -1 ) or F(ab′) 2 fragments of human immunoglobulin (1 g·kg -1 ·d -1 ) once the other day for 8 or 16 weeks.Sibling mice were injected intraperitoneally with human serum albumin (HSA) 1 g/kg once the other day as controls.16 weeks later, the mice were killed.Their blood in right atrium was extracted to examine the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG).The root of aorta and ascending aorta were isolated and made into tissue slices to be examined histochemically to calculate the areas of fatty streak and fibrofatty plaque.Immunohistological staining was conducted to examine the expression of macropdages CD+ 4 T cells and CD+ 8 T cell and infiltration of I-A b+ cells in the specimens of aorta roots.IG or F(ab′) 2 fragments and then lipopolysaccharide (LPS) was added into the culture media of cells of human monocyte/macrophage line U 937 carrying Fcγ receptor surface marker: CD 16 ,CD 32 ,and CD 64 molecules.Flow cytometry was used to detect the expression of these Fcγ receptor surface molecules. Results The area of fatty streak formation in the mice treated with IG was 4. 22.0%, significantly smaller than that in the control mice (13.6%±4.8%, P<0.01). However, the area of fatty streak formation in the mice treated with F(ab′) 2 fragments was 12.1%±3.7% , not significantly different from that of the controls. The area of fibrofatty plaque in the mice treated with IG was 8.1%±2.7%, significantly smaller than that of the control (21.5%±3.9%, P<0.01). However, the area of fibrofatty plaque in the mice treated with F(ab′) 2 frag

关 键 词：免疫球蛋白 动脉粥样硬化 载脂蛋白E类 免疫疗法 

分 类 号：R543.5[医药卫生—心血管疾病]