GDF11对高脂喂养ApoE-/-小鼠主动脉保护作用的研究  

Protective effect of growth differentiation factor 11 on aorta in ApoE-/-mice fed with high-fat diet

作　　者：梅稳[1] 向光大[1] 卢俊颜 李欢[1] 刘敏[1] 向林[1] 董靖[1] 

机构地区：[1]广州军区武汉总医院内分泌科,430070 [2]南方医科大学附属南方医院内分泌科

出　　处：《中华内分泌代谢杂志》2016年第7期594-601,共8页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金资助项目（81370896、81570730）

摘　　要：目的：探讨生长分化因子11（GDF11）对载脂蛋白E基因敲除（ApoE-/-）小鼠主动脉的作用及可能机制。方法4周龄健康雄性ApoE-/-小鼠适应性喂养1周后分为阳性对照组（Vehicle组,n=10）、GDF11干预组（ GDF11组, n=10）、腺相关病毒-绿色荧光蛋白组（ AAV-GFP 组, n=10）和腺相关病毒-GDF11组（AAV-GDF11组,n=10）。分别给予腹腔注射磷酸盐缓冲液、GDF11蛋白、尾静脉注射AAV-GFP和AAV-GDF11,干预4周后,测定血清GDF11/8浓度和血管内皮依赖性舒张功能。干预12周后,检测血清GDF11/8、白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）、总胆固醇（TC）、三酰甘油（TG）、氧化型低密度脂蛋白（ ox-LDL）及游离脂肪酸（ FFA）水平；油红O及苏木素伊红（ HE）染色分析主动脉粥样斑块表面积及横断面积；抗CD68和抗CD90免疫组化染色测定斑块巨噬细胞及T淋巴细胞浸润；实时定量PCR分析主动脉壁IL-6、TNF-α及IL-10等炎性因子mRNA水平。结果与对照组相比,GDF11和AAV-GDF11显著改善小鼠内皮依赖性舒张功能,降低血中炎性因子、血脂水平,减少动脉粥样斑块表面积[ Vehicle组：GDF11组：（31.23±3.12）%对（17.18±2.17）%；AAV-GFP组： AAV-GDF11组：（38.01±4.43）%对（14.54±2.86）%,P＆lt;0.05]及横断面积[Vehicle组： GDF11组：（19.87±2.11）%对（10.32±1.47）%；AAV-GFP组： AAV-GDF11组：（23.02±2.76）%对（9.06±1.63）%,P＆lt;0.05],减轻斑块内巨噬细胞及T淋巴细胞的浸润,降低主动脉壁炎性因子mRNA转录水平（均P＆lt;0.05）。结论 GDF11可减轻ApoE-/-小鼠主动脉粥样硬化病变,其机制可能与保护内皮、减轻炎症及改变斑块中细胞组成有关。Objective To investigate the effect of growth differentiation factor 11 （ GDF11 ） on aorta in apolipoprotein E-Null（ ApoE-/-） mice and its possible mechanisms. Methods Four-week-old healthy male ApoE-/-mice were fed with high-fat diet for 1 week and were then divided into 4 groups：vehicle group（n=10）, GDF11 group （n=10）,adeno-associated virus-green fluorescent protein group（AAV-GFP group, n=10）, and AAV-GDF11 group （ n=10 ） . The mice received intraperitoneal injection with phosphate buffered saline, GDF11 protein, a single injection of purified AAV-GDF11 or AAV-GFP through the tail vein, respectively. After 4 weeks, serum GDF11/8 level and endothelium-dependent vasodilatation were detected. After 12 weeks, serum GDF11/8, interleukin-6 （IL-6）, tumor necrosis factor-α（ TNF-α）, total cholesterol （ TC）, triglycerides （ TG）, oxidized low density lipoprotein（ox-LDL）, and free fatty acids（FFA）levels were measured, the plaque areas in aortic enface and cross sections were measured by oil red O or HE staining, the macrophages/T lymphocytes infiltration in plaques were detected with immunohistochemistry, and the mRNA expressions of IL-6, TNF-α, and IL-10 were determined by real-time PCR. Results Compared with vehicle or AAV-GFP groups, GDF11 and AAV-GDF11 groups presented improved endothelium-dependent vasodilatation, decreased levels of blood inflammatory factors, blood lipid, reduced plaque on face area sections[Vehicle group ： GDF11 group：（31. 23 ± 3. 12）% vs （17. 18 ± 2. 17） %;AAV-GFP group ： AAV-GDF11 group：（38.01±4.43）% vs（14.54±2.86）%,P〈0.05]andcrosssections[Vehiclegroup ：GDF11 group：（19. 87 ± 2. 11）% vs （10. 32 ± 1. 47）%;AAV-GFP group ： AAV-GDF11 group：（23. 02 ± 2. 76）%vs （9.06±1.63）%, P〈0. 05]. There were less macrophages and T lymphocytes infiltration in plaques and lower mRNA expressions of inflammatory factors at aortic wall. Conclusion GDF11 reduces the area of atherosclerotic＆amp;nbsp;lesion in

关 键 词：生长分化因子11 内皮依赖性舒张功能 炎症 动脉粥样硬化 

分 类 号：R543[医药卫生—心血管疾病]