非结核性分枝杆菌性兔角膜炎的研究

目的　探讨非结核性分枝杆菌（NTM）性兔角膜炎的临床表现与不同时期的病理变化。方法48只兔（48只眼）随机分为3组：角膜瓣下NTN感染组（UFI组）、角膜瓣下NTM感染后糖皮质激素使用组（UFIC组）及角膜表面NTM感染组（sI组）。观察角膜基质浸润情况,并于术后5、7、14及21d进行角膜病灶细菌定量培养、组织病理学及免疫组织化学检查。结果兔NTM角膜炎在感染后5d角膜组织反应性水肿;7—14d角膜浅基质层出现多灶性点、片状灰白致密浸润;21d角膜新生血管大量增生,白斑形成。术后5、7、14及21d,3组模型角膜基质浸润面积比较差异有统计学意义（F=19．224,P〈0．05）;组间比较,UFIC组角膜浸润面积大于UFI组与SI组,差异均有统计学意义（F=9．362,8．341;均P〈0．05）。角膜细菌定量培养,UFIC组细菌数量高于UFI组与SI组,3组间比较差异均有统计学意义（F=411．272,P〈0．05）。病理学观察,感染后5d角膜基质层大量中性粒细胞浸润,7～14d角膜淋巴细胞灶性浸润,21d角膜成纤维细胞和新生血管增生明显。3组模型于术后5、7、14及21d角膜组织中CD4’细胞计数差异均有统计学意义（F=21．907,196．521,12．552,11．100;均P〈0．01）,CD8^＋细胞计数在感染后7、14d差异均有统计学意义（E=171．115,77．017;均P〈0．01）。结论角膜基质多灶性点、片状灰白致密浸润为NTN性角膜炎临床特征,CD4^＋细胞介导的细胞免疫反应在本感染中起重要作用。（中华跟科杂志,2007,43：613-617）

Experimental study of non-tuberculous mycobacterial keratitis in rabbits

OBJECTIVE: To study clinical manifestation and pathology change of different time points of rabbit keratitis caused by non-tuberculous mycobacteria (NTM). METHODS: Forty-eight eyes from 48 rabbits were randomly divided into three groups:under-flap infection group (UFI group), under-flap infection group with corticosteroid (UFIC group) and surface infection group (SI group). The cornea infiltration area of all rabbits was observed. Bacterial quantitative culture and histopathological examination were performed. RESULTS: In the earliest stage (5 days), the cornea was cloudy and edematous. In the middle stage (7 - 14 days), cornea stromal infiltration became its major clinical sign. In the last stage (21 days), corneal neovascularization and fibrosis were developed. The mean stromal infiltration area in UFIC group was greater than those of UFI group and SI group (F = 9.362, 8.341, P < 0.05). The number of NTM in UFIC group was higher than those of UFI group and SI group (F = 411.272, P < 0.05). In histopathological examination, there were infiltrates with polymorphonuclear leukocytes (PMN) in the corneal stroma in the early stage and acid-fast bacilli was found. A plenty of lymphocytes in the cornea was found in the middle stage of NTM keratitis. In the latter stage, the fibroblast cells proliferation and corneal ulcer were cured. During the course of this infection, the number of CD4+, CD8+ T lymphocyte increased significantly, and then decreased gradually following the regress of the infection. In the stage (5 - 21 days), CD4+ T lymphocyte decreased significantly in UFIC group compared with other two groups (F = 21.907, 196.521, 12.552, 11.100, P < 0.01). CONCLUSIONS: The clinical characteristic of rabbit keratitis is the multifocal dense superficial stromal infiltrates. CD4+ T lymphocyte may play an important role in NTM keratitis.