大鼠佐剂性关节炎病程不同阶段T细胞亚群及重要器官的病理学变化

摘要

目的：观察大鼠佐剂性关节炎（adjuvantrheumatoidar-thritis，AA）病程不同阶段的脾脏T细胞亚群及其重要器官的病理学变化，探讨病程不同的阶段AA大鼠T细胞亚群变化的规律及局部组织和全身重要器官的病理学变化特点。方法选用20只♂Lewis大鼠，完全弗氏佐剂（CFA）诱导AA模型，造模后d7、d10、d13、d16、d19、d22进行全身评分和关节炎指数评分，计算关节肿胀数。造模后d14（炎症初期）、d22（炎症高峰期）处死大鼠，流式细胞仪检测炎症初期和炎症高峰期脾脏总T细胞（CD3＋CD4＋）、记忆T细胞（CD4＋CD44＋）、未致敏T细胞（CD4＋CD62L＋）的细胞亚群和Th17（CD4＋IL17＋）细胞亚群比例。d22取心、肝、脾、肺、肾、踝关节、肠系膜淋巴结组织，光镜观察各组织的病理学改变。结果大鼠免疫后10d出现继发侧足爪红肿，炎症初期（d10～d14）和炎症高峰期（d19～d22）AA大鼠的全身评分、关节炎指数评分和关节肿胀数有不同程度的增加。踝关节病理见滑膜组织增生、炎细胞浸润，血管翳出现等，且心、肝、脾、肺、肾、肠系膜淋巴结组织的病理也有不同程度的炎性变化。与正常组比较，炎症初期AA大鼠脾脏总T细胞、记忆T细胞和未致敏T细胞亚群比例都无明显变化、炎症高峰期AA大鼠脾脏总T细胞、记忆T细胞和未致敏T细胞亚群比例明显升高；Th17细胞亚群比例在炎症初期和高峰期都明显升高。结论AA大鼠的T细胞亚群在炎症初期和高峰期出现不同的变化特点；在大鼠AA不仅有关节局部的病理表现，且全身主要脏器组织均有受累。%Aim To observe the variation of T-cell subsets in spleen in different courses of disease and tis-sue histopathological changes in rats with adjuvant ar-thritis (AA).Methods The model of rat AA was in-duced by complete Freund’s adjuvant into the right hind metatarsal footpad of 20 male Lewis rats.Arthritis was evaluated by total score,arthritis index and paw swelling number. The percentage of total (CD3 +CD4 +), memory (CD4 + CD44 +), no-sensitizated (CD4 + CD62L +) and Th1 7 (CD4 + IL-1 7 +) on CD4 +T cells in spleen were detected by flow cytometry on days 1 4 and 22 after immuniozation.The his-topathological evaluation of heart,liver,spleen,lung, kidney,ankle joints and mesenteric lymph nodes were examined by hematoxylin and eosin (HE)stain.Re-sults The onset of secondary arthritis appeared on a-bout day 1 0 after immunization,with a peak onset on day 1 9.Systematic arthritis symptoms included front and hind paw swelling and redness (swelling was more apparent in the front rather than hind paws),nodule formation and redness on the ears,connective tissue swelling and redness of the nose and evident nodules and redness on the tail.Total score,arthritis index and the paw swelling numbers were enhanced in AA rats. Pathohistology of ankles joints showed hyperplasia, pannus formation,and inflammatory cells infiltration in AA rats.And pathohistology of heart,liver,spleen, kidney and mesenteric lymph nodes showed inflamma-tory changes.Compared with normal group,there was no change in the percentage of total,memory and no-sensitizated CD4 +T cell in the early stage inflammation but they were significantly enhanced in the peak of in-flammation.Th1 7 cell subsets were significantly en-hanced in both of the early and peak of inflammation. Conclusion These findings suggest that abnormal T cell responses and tissue histopathological changes are important features of AA rats.