一氧化碳释放分子对牙周炎大鼠动脉粥样硬化的影响

Effect of CORM-2 on atherosclerosis in experimental periodontitis of rats

目的:研究一氧化碳释放分子(carbon monoxide releasing molecule-2,CORM-2)对实验性大鼠牙周炎模型中动脉粥样硬化的作用。方法:40只8周龄Wistar大鼠,随机分为正常组、一氧化碳组(carbon monoxide group,CO组)、牙周炎组(chronic periodontitis group,CP组)和溶剂组(dimethylsulfoxide group,DMSO组)。CP组和CO组采用丝线结扎并注射内毒素法建立牙周炎模型。建模当天,CO组经腹腔注射CORM-2(10 mg/kg/d),DMSO组注射等体积DMSO溶液(0.05%V),正常组不做任何处理。分别于建模后1、3、7、14、28 d用酶联免疫吸附法检测血清内C反应蛋白(Creactive protein,CRP)、可溶性血管细胞黏附分子1(soluble vascular cell adhesion molecule-1,sVCAM-1)、氧化型低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)及白介素10(interleukin-10,IL-10)的含量。4周后处死大鼠,取大鼠降主动脉行油红O染色,观察脂质沉积情况,并检测牙槽骨吸收情况。采用SPSS 17.0软件包对所得数据进行统计学分析。结果:CO组大鼠牙周组织中炎细胞浸润及牙槽骨吸收程度均较CP组大鼠低,CP组大鼠血清CRP、sVCAM-1及ox-LDL水平显著高于CO组,CO组大鼠血清中IL-10水平显著高于其他各组(P<0.05)。28天后,在CP组大鼠降主动脉中可发现脂质沉积,而CO组大鼠血管中则无脂质沉积。结论:CORM-2能够抑制实验性牙周炎大鼠的炎性反应及动脉粥样硬化的形成。

PURPOSE： To evaluate the effect of CORM-2 （carbon monoxide releasing molecule-2） on atherosclerosis in experimental periodontitis of rats. METHODS： Forty Wistar rats were divided into four groups randomly. Rats in control group did not receive any procedure; animals in the carbon monoxide group （CO group） and the chronic periodontitis group （CP group） were induced experimental periodontitis and treated with CORM-2 （10mg/kg per day）, or normal saline solution （NaCl 0.9%）, respectively; animals in the solvent group （DMSO group） received dimethylsulfoxide solution （DMSO 0.05%） only. Blood samples were collected after 1, 3, 7, 14 and 28 days from all animals for analysis of C react protein （CRP）, oxidized low density lipoprotein （ox-LDL）, soluble vascular cell adhesion molecule-1, （sVCAM-1） and interleukin-10 （IL- 10） by enzyme-linked immunosorbent assay （ELISA）. Rats were sacrificed after 28 days. Lipid deposition was checked by means of oil red staining in the descending aorta. Changes in alveolar bone levels were measured and periodontal tissues were histopathologically examined to assess the infiltration of inflammatory cells. SPSS17.0 software package was used to analyse the experimental data. RESULTS： The serum levels of CRP, ox-LDL and sVCAM-1 in CP group were significantly higher than that in CO and the other two groups （P〈0.05）. The level of IL-10 in CP group was significantly lower （P〈0.05）. Lipid deposition in the descending aorta was observed in CP group. The alveolar bone loss and the ratio of presence of inflammatory cell infiltration （ICI） in CP group were significantly higher compared with CO groups （P〈0.05）. CONCLUSIONS： This study demonstrated that CORM-2 can not only reduce the inflammatory response in periodontaltissues in rats with experimental periodontitis, but also inhibit atherosclerosis-associated cytokines and lipid deposition in descending aorta, which suggests a favorable potential in treatment of periodontitis and atherosclerosis. Supported by Science and Technology Development Project of Shandong Province （2010GSF10270, 2012G0021833）.