A mouse model linking viral hepatitis and salivary gland dysfunction
A mouse model linking viral hepatitis and salivary gland dysfunction
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DOI：
10.1111/j.1601-0825.2009.01600.x
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发表时间：
2009-11-01
期刊：
影响因子：
3.8
通讯作者：
Pilgrim, M. J.
中科院分区：
文献类型：
--
作者：
Kasman, L. M.;London, L. L.;Pilgrim, M. J.
目的：病毒性肝炎可导致人类口干症，但在动物模型中尚未见报道。我们报道了BALB/c小鼠由于实验性病毒性肝炎而发生的严重的、急性的、高度可复制的唾液缺乏。材料和方法：BALB/c小鼠，切除脾或携带基因突变以检测唾液缺乏综合征的免疫学贡献，经腹腔感染非致死量的小鼠巨细胞病毒。在感染后0至15天内测定匹罗卡品刺激的唾液量。分析唾液腺、肝脏、脾和血清中病毒、细胞因子、炎性浸润物和组织损伤的存在。结果：巨细胞病毒感染后2天可检测到唾液缺乏，第7天唾液不足达正常水平的88%，感染后15天随着涎腺炎的加重，所有小鼠唾液不足部分消失。唾液腺病毒滴度、涎腺炎、脾切除或全身炎症标记物均与肺功能低下的严重程度无关。结论：巨细胞病毒诱导的小鼠唾液腺功能障碍是双相性的，急性肝炎相关阶段和涎腺炎相关阶段。小鼠急性巨细胞病毒感染BALB/c小鼠可能为研究肝炎相关性口干症提供了一种模型。
Objective:Viral hepatitis is known to cause xerostomia in humans, but this has not been reported in an animal model. We report a severe, acute, highly reproducible saliva deficiency occurring in BALB/c mice as a result of experimental viral hepatitis.Materials and Methods:BALB/c mice, splenectomized or carrying genetic mutations to detect immunological contributions to the saliva deficiency syndrome, were infected intraperitoneally with a non-lethal dose of murine cytomegalovirus. Pilocarpine-stimulated saliva volumes were determined between 0 and 15 days after infection. Salivary gland, liver, spleen, and sera were analyzed for the presence of virus, cytokines, inflammatory infiltrates, and tissue damage.Results:Saliva deficiency was detectable 2 days after cytomegalovirus infection, peaked at 88% below normal by day 7, and resolved partially in all mice by 15 days postinfection as sialoadenitis increased. Neither salivary gland viral titers, sialoadenitis, splenectomy, nor systemic inflammatory markers correlated with hyposalivation severity. Elevated liver enzymes did correlate with hyposalivation, and mice genetically resistant to murine cytomegalovirus-induced hepatitis were significantly protected.Conclusions:Murine cytomegalovirus-induced salivary gland dysfunction is biphasic, with an acute hepatitis-associated phase and a later sialoadenitis-associated phase. Acute murine cytomegalovirus infection of BALB/c mice may provide a model for investigation of hepatitis-associated xerostomia.