Brodala Nadine, Merricks Elizabeth P, Bellinger Dwight A, Damrongsri Damrong, Offenbacher Steven, Beck James, Madianos Phoebus, Sotres Daniela, Chang Yu-Ling, Koch Gary, Nichols Timothy C
School of Dentistry and Department of Periodontology, University of North Carolina at Chapel Hill and the Center of Oral and Systemic Diseases, Chapel Hill, NC 27516-3114, USA.
Arterioscler Thromb Vasc Biol. 2005 Jul;25(7):1446-51. doi: 10.1161/01.ATV.0000167525.69400.9c. Epub 2005 Apr 21.
The aim of this study was to determine whether recurrent intravenous injections with Porphyromonas gingivalis (P gingivalis), mimicking periodontitis-associated bacteremia, promotes coronary artery and aortic atherosclerosis in pigs.
Pigs (n=36) fed low- or high-fat chow were divided into P gingivalis-sensitized and P gingivalis-challenged groups or P gingivalis-sensitized controls and saline-treated controls. Pigs were sensitized with 10(9) killed P gingivalis subcutaneously. Four weeks later all sensitized pigs in the group to be challenged started intravenous injections thrice weekly for 5 months with 10(6) to 10(7) colony forming units of P gingivalis while controls received saline. Anti-P gingivalis antibody, serum cholesterol, and complete blood counts were assayed monthly. Pigs were euthanized 2 weeks after the last injection, and coronary arteries and aortas were analyzed by histomorphometry and immunohistochemistry. Anti-P gingivalis antibody was increased by P gingivalis exposure. P gingivalis-challenged pigs developed a significantly greater amount of coronary and aortic atherosclerosis than controls in the normocholesterolemic group and nearly significant in the hypercholesterolemic group. P gingivalis was detected by polymerase chain reaction in arteries from most (94%, 16 of 17) P gingivalis-challenged pigs but not controls.
Recurrent P gingivalis bacteremia induces aortic and coronary lesions consistent with atherosclerosis in normocholesterolemic pigs and increases aortic and coronary atherosclerosis in hypercholesterolemic pigs.
本研究旨在确定反复静脉注射牙龈卟啉单胞菌(P gingivalis),模拟与牙周炎相关的菌血症,是否会促进猪的冠状动脉和主动脉粥样硬化。
将喂食低脂或高脂食物的猪(n = 36)分为牙龈卟啉单胞菌致敏组和牙龈卟啉单胞菌激发组,或牙龈卟啉单胞菌致敏对照组和生理盐水处理对照组。猪皮下注射10⁹ 灭活的牙龈卟啉单胞菌进行致敏。四周后,所有待激发组的致敏猪开始每周静脉注射三次,持续5个月,每次注射10⁶ 至10⁷ 菌落形成单位的牙龈卟啉单胞菌,而对照组注射生理盐水。每月检测抗牙龈卟啉单胞菌抗体、血清胆固醇和全血细胞计数。在最后一次注射后2周对猪实施安乐死,通过组织形态计量学和免疫组织化学分析冠状动脉和主动脉。牙龈卟啉单胞菌暴露使抗牙龈卟啉单胞菌抗体增加。在正常胆固醇血症组中,牙龈卟啉单胞菌激发组的猪发生的冠状动脉和主动脉粥样硬化明显多于对照组,在高胆固醇血症组中差异接近显著。在大多数(94%,17只中的16只)牙龈卟啉单胞菌激发组猪的动脉中通过聚合酶链反应检测到牙龈卟啉单胞菌,而对照组未检测到。
反复的牙龈卟啉单胞菌菌血症在正常胆固醇血症猪中诱导出与动脉粥样硬化一致的主动脉和冠状动脉病变,并增加高胆固醇血症猪的主动脉和冠状动脉粥样硬化。