泪腺作为潜在人免疫缺陷病毒储存库的分子机制研究  

A pilot molecular mechanism study on lacrimal gland as a potential human immunodeficiency virus reservoir

作　　者：刘子扬[1] 刘小伟[1] 叶俊杰[1] 韩扬[2] 霍真[3] 

机构地区：[1]中国医学科学院 北京协和医学院 北京协和医院眼科,北京100730 [2]中国医学科学院 北京协和医学院 北京协和医院感染科,北京100730 [3]中国医学科学院 北京协和医学院 北京协和医院病理科,北京100730

出　　处：《中华实验眼科杂志》2017年第5期410-415,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目（81371758）

摘　　要：背景获得性免疫缺陷综合征（AIDS）是由人类免疫缺陷病毒（HIV）感染引起的以全身免疫系统严重损害为特征的感染性疾病，目前主要的治疗方法是高效抗逆转录病毒疗法（HAART），但不能彻底清除患者体内的免疫缺陷病毒（HIV），目前认为是病毒潜伏于HIV储存库所致。研究证实HAART治疗后患者血浆中HIV载量检测阴性的AIDS患者的泪液中发现了HIV，因此探索其眼部储存库是非常重要的。目的探讨泪腺组织是否具有HIV储存库的分子基础以及HIV感染泪腺组织的发生机制。方法收集2013年11月至2015年12月在北京协和医院因泪腺良性疾病行泪腺手术获得的泪腺组织标本14例，其中13例来自于HIV阴性患者，1例来自于HIV阳性患者。13例HIV阴性患者临床诊断为泪腺脱垂者9例和泪腺炎者4例，病理诊断为正常泪腺组织者12例和泪腺间质淋巴组织增生者1例。HIV阳性患者的临床诊断为泪腺炎，病理诊断为泪腺间质淋巴组织增生。将12例HIV阴性和1例HIV阳性患者的泪腺组织标本用石蜡固定切片，采用免疫组织化学法检测泪腺标本中HIV受体CD4及CXC趋化因子受体4（CXCR4）和CC趋化因子受体5（CCR5）分子的表达；1例HIV阴性患者的泪腺组织标本制备成新鲜冰冻切片，采用免疫荧光染色对泪腺标本中CD4及CXCR4和CCR5分子的表达进行验证。结果免疫组织化学染色显示，HIV阴性患者泪腺组织CD4分子染色背景强，为可疑阳性表达；各例标本中多数泪腺上皮细胞可见CXCR4表达，定位于细胞质和细胞核，少数泪腺上皮细胞不表达CXCR4；在各例标本中少数泪腺上皮细胞中CCR5呈局灶阳性表达，主要位于细胞质和细胞核，多数泪腺上皮细胞不表达CCR5。HIV阳性患者泪腺组织中CD4分子染色背景强，为可疑阳性表达；CXCR4及CCR5在泪腺上皮细胞中为阳性表达；间质组织中可见大量散在淋巴细胞，其CD4BackgroundAcquired immune deficiency syndrome （AIDS） is an infectious disease caused by human immunodeficiency virus （HIV）. Highly active antiretroviral therapy （HAART） is an effective treatment for AIDS, but it cannot completely eliminate the viral load in the body for the existence of HIV reservoir.Previous studies demonstrated that HIV could be detected in tears of virus load negative AIDS patients who received effective HAART, suggesting that lacrimal gland is another member of HIV reservoirs.ObjectiveThe aim of this study was to explore whether lacrimal gland has a molecular basis of HIV infection and the mechanism of lacrimal gland infection of HIV.MethodsFourteen specimens of lacrimal gland were collected during the surgery from 14 patients with lacrimal gland diseases in Peking Union Medical College Hospital from November 2013 to December 2015, including 13 non-HIV-infected patients and 1 HIV-infected patient.In 13 non-HIV infected patients, lacrimal glands prolapse was in 12 patients with the normal pathological tissue structure and dacryoadenitis was in 1 patient with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The clinical manifestation of HIV-infected patient was dacryoadenitis with the histopathological diagnosis of interstitial lymphoid tissue hyperplasia.The paraffin sections of 12 non-HIV-infected specimens and 1 HIV-infected specimen were prepared, and the expressions of CD4, C-X-C chemokine receptor 4 （CXCR4）and C-C chemokine receptor type 5 （CCR5） in lacrimal gland specimens were detected by immunohistochemistry and verified in 1 specimen of non-HIV-infected specimen by immunofluorescence technology.ResultsImmunohistochemistry showed that CD4 was suspiciously positive expression in non-HIV-infected specimens with the strong background staining.CXCR4 was positively expressed in cytoplasm and nuclei of most lacrimal epithelial cells of lacrimal gland epithelial cells in each specimen, and CCR5 was focally expressed in few lacrimal gland epitheli

关 键 词：获得性免疫缺陷综合征/免疫学 艾滋病相关眼病/代谢 人免疫缺陷病毒感染/代谢 病毒潜伏 泪液/病毒学 CD4^+T淋巴细胞受体/病毒学 CXCR4受体/代谢 CCR5受体/代谢 泪腺上皮细胞 

分 类 号：R512.91[医药卫生—内科学]