血管壁Meprin-α调控活性氧生成影响小鼠腹主动脉瘤形成的实验研究  

Effect of active oxygen production in intravascular wall regulated by Meprin-α on formation of abdominal aortic aneurysm in mice

作　　者：谭志晖 吴秀琳 章陈晨 司良毅 郜攀 Tan Zhihui;Wu Xiuling;Zhang Chenchen;Si Liangyi;Gao Pan(Department of Geriatrics,920th Hospital PLA,Kunming 650032,Yunnan Province,China)

机构地区：[1]解放军联勤保障部队第九二○医院军干病房,昆明650032 [2]陆军军医大学第一附属医院老年医学科

出　　处：《中华老年心脑血管病杂志》2019年第1期53-57,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81370007);重庆市基础与前沿研究计划(cstc2016jcyjA0072)

摘　　要：目的探讨血管壁内Meprin-α调控活性氧生成的作用对小鼠腹主动脉瘤(abdominal aortic aneurysm,AAA)形成影响的实验研究。方法选择8～10周龄雄性载脂蛋白E(apo E)-po小鼠12只随机分为假手术组(Sham组,置入生理盐水的缓释泵)和apo E-po模型组(SKO组,置入血管紧张素Ⅱ缓释泵),同时另取apo E-poMep1a-ep小鼠6只(DKO组,置入血管紧张素Ⅱ缓释泵)构建小鼠AAA动物模型。4周后取材,检测腹主动脉最大直径以及AAA发生率,分析各组主动脉形态学变化、血管壁活性氧生成情况及腹主动脉Meprin-α、表皮生长因子受体(EGFR)及磷酸化EGFR(p-EGFR)蛋白表达水平。结果 SKO组血管壁出现明显的内膜、肌纤维细胞增生,且血管弹力蛋白结构被明显破坏; DKO组内膜和肌纤维细胞增生程度不明显,且血管弹力蛋白结构破坏程度较轻。Sham组未见腹主动脉管径扩张,与Sham组比较,SKO组小鼠腹主动脉最大直径显著增高[(1. 22±0. 15) mm vs (0. 45±0. 04)mm)],腹主动脉血管壁活性氧(9285±1149 vs 1836±352)水平明显增多,Meprin-α及p-EGFR蛋白表达显著升高,差异有统计学意义(P <0. 05);与SKO组比较,DKO组小鼠腹主动脉最大直径显著降低[(0. 65±0. 10) mm vs (1.22±0. 15) mm]、腹主动脉血管壁活性氧(5981±557 vs 9285±1149)、Meprin-α及p-EGFR蛋白表达显著降低,有统计学差异(P <0. 05)。3组EGFR蛋白表达比较,无统计学差异(P> 0. 05)。结论抑制小鼠Meprin-α蛋白可显著抑制AAA形成,其作用机制可能与抑制Meprin-α蛋白使p-EGFR表达下调,进而阻断氧化应激作用密切相关。Objective To study the effect of active oxygen production regulated by Meprin-αin intravascular wall on formation of abdominal aortic aneurysm(AAA)in mice.Methods Twelve 8-10 weeks old male apoE-po mice were randomly divided into sham operation group(n=6 into whom a normal saline slow-release pump was placed)and apoE-po model group or SKO group(n=6 into whom an angiotensinⅡslow-release pump was placed).Another 6 apoE-ep mice served as a DKO group into whom an angiotensinⅡslow-release pump was placed to establish a mouse AAA model.The longest AAA diameter was measured and the incidence of AAA was recorded after 4 weeks.Results Tunica intima,proliferation of muscle fibrous cells and vasoelastic protein structure damage were detected in vascular wall of SKO group.No visible tunica intima and proliferation of muscle fibrous cells were detected in DKO group with mild damage of vasoelastic protein structure.No dilatation of abdominal aorta was found in sham operation group.However,the longest AAA diameter was significantly longer in SKO group than in sham opera-tion(1.22±0.15 mm vs 0.45±0.04 mm,P<0.05).The expression levels of active oxygen,Me-prin-αand p-EGFR were significantly lower in DKO group than in SKO group(P<0.05).No significant difference in EGFR expression was found in 3 groups(P >0.05).Conclusion Inhibition of Meprin-αcan significantly reduce the formation of AAA by downregulating the expression of Meprin-αand p-EGFR,and blocking the oxidative stress.

关 键 词：受体 表皮生长因子 主动脉瘤 腹 载脂蛋白E类 活性氧 血管紧张素Ⅱ 动脉粥样硬化 

分 类 号：R543.16[医药卫生—心血管疾病]