Brunson Jerry L, Becker Felix, Stokes Karen Y
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Center for Molecular and Tumor Virology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Center for Cardiovascular Disease and Sciences, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States.
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71130, United States; Department of General and Visceral Surgery, University Hospital Muenster, Germany.
Pathophysiology. 2015 Mar;22(1):31-7. doi: 10.1016/j.pathophys.2014.11.001. Epub 2014 Nov 18.
Cytomegalovirus (CMV) infects 60-100% of the population worldwide. CMV has been implicated in many diseases through the induction of inflammation. Inflammatory bowel disease (IBD) affects over 1 million Americans annually. IBD, in particular ulcerative colitis, has been associated with CMV infection. Here we use a murine model to test if both primary and persistent CMV infections exacerbate colitis. C57Bl/6J mice were injected with Mock inoculum or murine CMV (mCMV) 4d (primary infection) or 6wks (persistent infection) before inducing colitis. Colitis was induced by administering 3% DSS (dextran sodium sulfate) in the drinking water for 6 days. Distilled water was given to controls. Disease activity index (DAI), derived from scores for stool consistency, body weight loss, occult blood, and rectal bleeding, was recorded daily. DAI increased early with DSS treatment in Mocks when compared with water-treated controls. This was accelerated by both primary and persistent mCMV and appeared to be primarily due to the earlier appearance of gross bleeding vs. their Mock controls. Mocks reached similar DAI values by day 6. Myeloperoxidase was modestly elevated in the mCMV 4d-DSS over the Mock 4d-DSS, however there was no such synergism in the 6wk groups. Histology was comparable in Mock and mCMV groups. Taken together our findings show that mCMV accelerated the development of acute colitis although a milder model of colitis may be needed to better delineate the impact of the virus on disease progression. Further work focusing on disruption of barrier function and bleeding may help determine the underlying mechanisms.
巨细胞病毒（CMV）感染了全球60%-100%的人口。CMV通过引发炎症与多种疾病相关。炎症性肠病（IBD）每年影响超过100万美国人。IBD，尤其是溃疡性结肠炎，已与CMV感染有关。在此，我们使用小鼠模型来测试原发性和持续性CMV感染是否都会加重结肠炎。在诱导结肠炎前4天（原发性感染）或6周（持续性感染），给C57Bl/6J小鼠注射模拟接种物或鼠巨细胞病毒（mCMV）。通过在饮用水中给予3%右旋糖酐硫酸钠（DSS）6天来诱导结肠炎。给对照组饮用蒸馏水。每天记录源自粪便稠度、体重减轻、潜血和直肠出血评分的疾病活动指数（DAI）。与水处理对照组相比，模拟组在DSS处理后DAI早期升高。原发性和持续性mCMV均加速了这一过程，这似乎主要是由于与模拟对照组相比，肉眼可见出血出现得更早。模拟组在第6天达到了相似的DAI值。与模拟4天-DSS组相比，mCMV 4天-DSS组髓过氧化物酶略有升高，然而在6周组中没有这种协同作用。模拟组和mCMV组的组织学表现相当。综合我们的研究结果表明，mCMV加速了急性结肠炎的发展，尽管可能需要一个更温和的结肠炎模型来更好地描述病毒对疾病进展的影响。专注于屏障功能破坏和出血的进一步研究可能有助于确定潜在机制。
