摘要
目的探讨3种干燥综合征(Sjögren's syndrome,SS)小鼠造模方式在临床症状、病理改变、炎症指标等方面的差异。对比研究临床症状、病变相关组织的病理改变、炎症因子表达情况。方法将30只C57BL/6J雌性小鼠根据随机数字表法分为3组,即正常组、N49组和颌下腺组,每组各10只。另外10只非肥胖型糖尿病重症联合免疫缺陷(NOD-scid)雌性小鼠则为NOD组。分别采用非肥胖型糖尿病(non-obese diabetic,NOD)小鼠自发、毒蕈碱受体3(muscarinic receptor 3,M3R)抗原表位多肽N49免疫诱导与颌下腺蛋白诱导构建小鼠干燥综合征模型,定期监测饮水量、唾液流量,造模结束时取病理组织做HE染色观察淋巴细胞浸润程度,眼球取血检测炎症因子表达水平。结果(1)造模5周后,与正常组相比,各造模组小鼠饮水量显著增长(P<0.01);3个选模组组间比较,差异有统计学意义(P<0.01)。(2)造模5周后,与正常组相比,各造模组唾液流量显著减少(P<0.01);N49组、颌下腺组两组唾液流量均低于NOD组,差异具有统计学意义(P<0.05)。(3)造模5周后,与正常组相比,N49组、颌下腺组小鼠颌下腺指数、胸腺指数、脾指数上升较明显(P<0.01);颌下腺组与NOD组颌下腺指数相比差异有统计学意义(P<0.05)。N49组、颌下腺组与NOD组相比,胸腺指数上升较明显,差异有统计学意义(P<0.01)。(4)造模5周后,颌下腺病理切片观察显示,仅见颌下腺组有淋巴细胞浸润;各造模组胸腺和脾均有损害,但差异不大。(5)造模5周后,与正常组相比,NOD组、N49组、颌下腺组IL-10和IL-17水平升高(P<0.05或P<0.01),颌下腺组与NOD组相比,IL-10和IL-17水平升高(P<0.01),颌下腺组与N49组相比,IL-10水平升高(P<0.05),IL-17表达水平更高(P<0.01),差异有统计学意义。结论相较于NOD模型和N49模型,颌下腺模型造模成本低,免疫反应起效快,症状更类似于人类SS,优点较为突出,可用于人类SS发病机制的研究和治疗药物的筛选。
Objective To explore the differences of clinical symptoms,pathological changes and inflammatory indexes among three mouse models of Sjögren's syndrome(SS).The clinical symptoms,pathological changes of lesion-related tissues and the expression of inflammatory factors were compared.Methods Thirty C57BL/6J female mice were randomly divided into three groups using a random number table method,normal group,N49 group,and submandibular gland group,with 10 mice in each group.The other 10 NOD-scid female mice were in the NOD group.The mouse model of SS was established by immunizing NOD mice with spontaneity,polypeptide N49 of muscarinic receptor 3(M3R)epitope and submandibular gland protein,respectively.The amount of drinking water and saliva flow were monitored regularly.At the end of the model,the pathological tissue was taken for HE staining to observe the degree of lymphocyte infiltration,and the eyeball blood was taken to detect the expression level of inflammatory factors.Results(1)After 5 weeks,the amount of drinking water in each model group was significantly higher than that in the normal group(P<0.01),and there was significant difference between N49 group,submandibular gland group and NOD group(P<0.01).(2)At 5 weeks,compared with the normal group,the saliva flow in each model group was significantly decreased(P<0.01),and the saliva flow in N49 group and submandibular gland group was significantly lower than that in NOD group(P<0.05).(3)At 5 weeks,compared with the normal group,the submandibular gland index,thymus index and spleen index in N49 group and submandibular gland group increased significantly(P<0.01),and there was significant difference between submandibular gland group and NOD group(P<0.05).Compared with NOD group,the thymus index of N49 group and submandibular gland group increased significantly(P<0.01).(4)At 5 weeks,in the observation of pathological sections of submandibular gland,there was only lymphocyte infiltration in submandibular gland group,and there was damage to thymus and spleen in each model group,but there was no significant difference.(5)At 5 weeks,compared with the normal group,the levels of IL-10 and IL-17 in NOD group,N49 group,and submandibular gland group were slightly higher(P<0.05 or P<0.01),the levels of IL-10 and IL-17 in submandibular gland group were significantly higher than those in NOD group(P<0.01),IL-10 was slightly higher(P<0.05),and IL-17 expression was higher(P<0.01)in submandibular gland group than that in N49 group,with statistically significant.Conclusion Compared with NOD model and N49 model,submandibular gland model has lower cost,immune response takes effect quickly and more similar symptoms to human SS.It can be used to study the pathogenesis of human SS and screen therapeutic drugs.
作者
张苏丹
王妍琦
刘亚伟
杨双庆
孟庆良
马俊福
ZHANG Sudan;WANG Yanqi;LIU Yawei;YANG Shuangqing;MENG Qingliang;MA Junfu(Henan University of Traditional Chinese Medicine,Zhengzhou 450046,Henan,China;Henan Provincial Hospital of Traditional Chinese Medicine,Zhengzhou 450002,Henan,China)
出处
《辽宁中医药大学学报》
CAS
2024年第12期99-103,共5页
Journal of Liaoning University of Traditional Chinese Medicine
基金
国家自然科学基金(81804050)
河南省中医药科学研究专项重大课题(20-21ZYZD05)
河南省中医药专项项目(2019ZY1018)
河南省中医药专项项目(2019ZY2032)
河南省中医药拔尖人才培养项目。
关键词
干燥综合征
动物模型
NOD小鼠自发
毒蕈碱受体3
抗原表位多肽
颌下腺蛋白
Sjögren's syndrome
animal model
NOD mouse spontaneity
muscarinic receptor 3
antigenic epitope peptide
submandibular gland protein model
