ANCA相关性血管炎存在血管内皮细胞血栓调节蛋白以及内皮源性一氧化氮合酶弥漫性丢失

摘要

Objective To investigale the expression features of endothelial-nitric oxide synthase and thrombomod-ulin in vascular endothelium of the arteriolar and venule wall in patients with ANCA associated vasculitis. Methods We collected 12 patients with ANCA associaled vasculitis confirmed by clinical and serum immunological diagnosis, including 2 cases of Wegerner granulomatosis, 5 cases of microscopic polyangiitis and 5 cases of Churg-Strause syndrome. Sural nerve biopsies were made in all palienls. The specimens were stained with routine histological and immunohistological stainings with first antibodies aganist CD 68, CD 20, CD 4, von Willebrand Factor, the endothelial-nitric oxide synthase (eNOS) and the thrombomodulin ( TM). Results Nine of 12 palients with active vasculitis had numerous CD68 positive macro-phage and CD3 positive T-lymphocytes infiltrating. Compared with the normal control, the expression of eNOS and TM were significantly decreased or totally disappeared in the vascular endothelium of capillaries, arterioles and venuels, including the vessel without inflammatory infiltrating. The reduction in eNOS and TM expression were more obvious in Churg-Slrause syndrome among three types of AAV. The decrease in eNOS expression was more profound than TM. Conclusions There is diffuse reduction of eNOS and TM expression in vascular endolhelium in palients with AAV and the reduction varies among three types of AAV.%目的 探索ANCA相关性血管炎(antineutrophil cytoplasmic antibody-associated vasculitis,AAV)微小动脉和静脉的血管内皮细胞膜结合性血栓调节蛋白(thrombomodulin,TM)、内皮源性一氧化氮合酶(endothelial-nitric oxide synthase,eNOS)的表达规律.方法 12例经过临床、血清免疫学检查证实的AAV患者,2例Wegerner肉芽肿、5例显微镜下多血管炎和5例Churg-Strause综合征.Birmingham血管炎活动评分提示疾病处于活动期.均进行腓肠神经活检标本的常规组织学染色以及以抗CD68、CD3、CD20、血栓调节蛋白(thrombomodulin,TM)、eNOS以及第八因子(von Willebrand factor,vWF)抗体为第一抗体的免疫组织化学染色,以正常血管为对照.结果 12例患者的腓肠神经病理检查发现9例活动性血管炎,可见大量CD68阳性单核细胞和CD3阳性淋巴细胞浸润.和对照组相比,所有患者微小动脉和毛细血管内皮细胞eNOS和TM减低或消失,包括无炎细胞浸润血管,其中eNOS的下降程度较TM更明显.Churg-Strause综合征的血管内皮细胞eNOS和TM下降最显著.结论 AAV外周血管存在血管内皮细胞TM和eNOS弥漫性下降,两者下降程度在AAV不同亚型之间存在差异.