强直性脊柱炎食蟹猴膝关节及肠道组织病理变化分析  

Pathological changes in the knee joint and intestinal tissue in ankylosing spondylitis monkeys

作　　者：黄玉叶 蔡艳贞 蔡春梅 祝合朋 丁煌冠 贾欢欢[2] 肖文德[3] 陈珺[1] 李文德[2] 卢丽[1] HUANG Yuye;CAI Yanzhen;CAI Chunmei;ZHU Hepeng;DING Huangguan;JIA Huanhuan;XIAO Wende;CHEN Jun;LI Wende;LU Li(Guangdong Pharmaceutical University,Guangzhou 511400;China.2.Guangdong Laboratory Animals Monitoring Institute(Guangdong Provincial Key Laboratory of Laboratory Animals),Guangzhou 510663;.3.Guangzhou First People’s Hospital,Guangzhou 510180)

机构地区：[1]广东药科大学,广州511400 [2]广东省实验动物监测所(广东省实验动物重点实验室),广州510663 [3]广州市第一人民医院,广州510180

出　　处：《中国实验动物学报》2023年第10期1287-1295,共9页Acta Laboratorium Animalis Scientia Sinica

基　　金：2021年国家重点研发计划(2021YFF0702605);广东省自然科学基金(2022A1515010014,2023A1515010470);2021年广州市南沙区民生科技计划项目(2021MS002)。

摘　　要：目的 强直性脊柱炎(ankylosing spondylitis, AS)是一种免疫介导的累及中轴关节、周围关节和肠道的慢性疾病,但外周膝关节和肠道的病因病机未明。本研究旨在研究AS食蟹猴膝关节和肠道主要病理变化及机制。方法 通过组织形态学分析及免疫组化实验,研究AS外周膝关节及肠道组织的关键特征并初步分析其发病机制。结果 AS食蟹猴外周膝关节病理特征在早期主要表现为关节表面软骨侵蚀、软骨下骨暴露、关节表面呈锯齿状;晚期主要表现为软骨表层肥大软骨细胞异位增生,通过软骨成骨和纤维成骨形成骨赘,软骨基本丢失。软骨和血管中MMP-3的表达上调,引起软骨破坏并刺激血管增生。AS食蟹猴小肠绒毛严重萎缩且隐窝增生明显,空肠和回肠的黏膜肠腺中可见大量γδT细胞。结论 本研究通过对AS食蟹猴膝关节和肠道的病理分析,获得了该自发模型膝关节与肠道组织的关键特征,并提出可能的发病机制。为探讨AS的骨骼病变与外周疾病间的潜在关联,以及AS的治疗提供新的见解。Objective Ankylosing spondylitis(AS)is an immune-mediated chronic disease involving axial joints,peripheral joints,and intestines,but the etiology of peripheral knees and intestines is unknown.This study examined the main pathological changes and mechanisms of knee joints and intestines in cynomolgus monkeys with AS.Methods The main characteristics of peripheral knee joint and intestinal tissues of AS were examined and the possible pathogenesis was preliminarily analyzed by histomorphology and immunohistochemistry.Results The pathological characteristics of peripheral knee joints in AS cynomolgus monkeys were mainly cartilage erosion on the joint surface,exposed subchondral bone,and a jagged joint surface in the early stage.In the late stage,the knee joints mainly manifested as ectopic hyperplasia of cartilage superficial hypertrophy of chondrocytes,osteophytes formed through chondrogenesis and fibrogenesis,and loss of cartilage.MMP-3 expression in cartilage and blood vessels was upregulated,causing cartilage destruction and stimulating angiogenesis.AS cynomolgus monkeys had severe atrophy of small intestinal villi and obvious crypt hyperplasia,and a large number ofγδT cells was seen in the mucosal intestinal glands of the jejunum and ileum.Conclusions Pathological analysis of knee joints and intestines in AS cynomolgus monkeys revealed their main characteristics in this spontaneous model and suggested the possible pathogenesis.This study provides new insights into the potential link between autoimmunity in bone tissue and intestinal tissue lesions in AS.

关 键 词：强直性脊柱炎 食蟹猴 膝关节 基质金属酶3 

分 类 号：Q95-33[生物学—动物学]