阿托伐他汀、替硝唑对动脉粥样硬化合并牙周炎兔心肌内TNF-α、IL-1、MMP-2的影响  

Impacts of atovastatin and tinidazole on cardiac muscle inflammation factors of tumor necrosis factor-α, interleukin-1 and metalloproteinase-2 of experimental rabbits with atherosclerosis andpe^odonfifis

作　　者：张元[1] 张源明[1] 梁平[1] 侯秀丽[1] 

机构地区：[1]新疆医科大学第一附属医院心脏中心高血压科,乌鲁木齐830054

出　　处：《中华医学杂志》2013年第8期610-613,共4页National Medical Journal of China

基　　金：国家自然科学基金（30960135）

摘　　要：目的探讨阿托伐他汀、替硝唑控制动脉粥样硬化及对牙周炎肿瘤坏死因子（TNF）α、白细胞介素（IL）-1及基质金属蛋白酶（MMP）-2的影响。方法48只雄性新西兰大白兔随机数字表法分为4组：对照组（A组）、阿托伐他汀组（B组）、替硝唑组（C组）、联合干预组（阿托伐他汀＋替硝唑，D组），每组12只。各组分别按照实验设计进行相应干预处理：第1～4周进行新西兰大白兔的下颌第一前磨牙结扎，建立牙周炎模型，第1周先以50％高脂饲料＋50％普通饲料进行适应性喂养，之后改为全高脂饲料喂养，建立动脉粥样硬化模型，实验第16～20周进行药物干预灌胃给药（每周2次）：A组给予同体积生理盐水，B组给予阿托伐他汀片1．5mg／kg，C组给予替硝唑片150mg／kg，D组给予阿托伐他汀片1．5mg／kg＋替硝唑片150mg／kg。至20周末处死动物，取血管及心肌组织，采用免疫组化技术及荧光定量PER技术进行定量测定。结果MMP-2表达的阳性面积，B组、C组及D组均小于A组，差异均有统计学意义（35％±17％、69％±5％、30％±7％比86％±9％，均P〈0．05），D组最小，与其他3组差异均有统计学意义（均P〈0．05）。荧光定量PCR结果显示，4组中TNF-α和IL-1的表达，B组、C组及D组均低于A组，且D组均最低（均P〈0．05）。结论阿托伐他汀、替硝唑可以降低动脉粥样硬化合并牙周炎兔TNF-α、IL-1及MMP-2的表达量且两药物联合应用效果更佳。Objective To explore the effects of atovastatin and tinidazole on atherosclerosis and the levels of tumor necrosis factor-α （TNF-α）, interleukin-1 （IL-1） and matrix metalloproteinase-2 （ MMP-2 ） in periodontitis. Methods A total of 48 male New Zealand white rabbits were randomly divided into 4 groups （n = 12 each）： control group （A）, atovastatin group （B）, tinidazole group （C） and combination group （ D, atovastatin ＋ tinidazole）. All groups received interventions according to the experiment design. During Week 1 - 4, mandibular first premolars were used to establish periodontitis model. For Week 1, adaptive feeding was provided with 50% normal diet ＋ 50% high-fat diet. Then a full high fat-diet was used to establish atherosclerosis model. During Week 16 -20, experimental drug intervention was administered twice weekly： group A received the same volume of saline, group B atorvastatin tablets 1.5 mg/kg, group C tinidazole tablets 150 mg/kg and group D atorvastatin tablets 1.5 mg/kg ＋ tinidazole tablets 150 mg/kg. At the end of 20-week intervention, the animals were sacrificed to take vascular and heart tissue samples. Immunohistochemistry and fluorescent polymerase chain reaction （PCR） were employed for quantitative determinations. Results The positive areas of MMP-2 expression in groups B, C and D were smaller than that of group A respectively （35% ± 17%, 69% ±5 %, 30%± 7% vs 86% ±9%, all P 〈 0. 05 ）. And the PCR results showed the levels of TNF-α and IL-1 in group D was the lowest of four groups （ all P 〈 0.05 ）. Conclusion Atovastatin and tinidazole can reduce the expression levels of TNF-α, IL-1 and MMP-2 in therabbits with atherosclerosis and periodontitis respectively. And the combination of both drugs may achieve a better efficacy.

关 键 词：动脉粥样硬化 牙周炎 阿托伐他汀 替硝唑 

分 类 号：R543.5[医药卫生—心血管疾病]