口腔干预措施对伴动脉粥样硬化的慢性牙周炎大鼠颈动脉壁及血清C反应蛋白、白介素6的影响

Effects of oral interventions on carotid artery, serum C-reactive protein and interleukin 6 in chronic periodontitis rats with atherosclerosis

目的 通过研究伴动脉粥样硬化（atherosclerosis,As）的慢性牙周炎（chronic periodontitis,CP）大鼠模型中颈动脉血管的病理变化及血清C反应蛋白（C-reactive protein,CRP）、白介素6（interleukin 6,IL-6）的表达情况,探讨不同口腔干预措施对As的影响.方法 44只清洁级SD大鼠按随机数字表法随机分为A组（正常对照组,7只）、B组（As组,8只）和C组（CP＋As组,29只）.按随机数字表法处死B组及C组大鼠各1只,制作血管冰冻切片,证明As建模成功.将C组再按随机数字表法分为4组（C1组：自然进程组,C2组：机械治疗组,C3组：药物治疗组,C4组：拔牙治疗组）,每组7只,对各组大鼠进行相应的口腔干预,分别于干预前1周、第1次干预后1周、第2次干预后1、3、5周尾静脉采血,酶联免疫吸附测定法检测血清CRP、IL-6的浓度,HE染色,光镜下观察颈动脉分叉处血管的病理变化.结果 C1、C4组可见大量炎症细胞黏附和泡沫细胞形成,弹性纤维排列紊乱断裂,管壁有钙盐沉积;C2组血管壁未见明显增厚,弹性纤维排列较整齐;C3组血管壁薄厚不一,泡沫细胞广泛,弹性纤维排列较紊乱;血清学结果显示口腔干预前后血清CRP、IL-6呈现出相同的变化趋势.在所有取样时间点,B组和C组的CRP、IL-6含量均显著高于A组（P〈0.01）;随时间推移,B组和C1组血清CRP、IL-6含量一直升高,在干预后所有时间点,血清含量与其各自基线水平相比差异均有统计学意义（P〈0.05）,在最后的检测时间点,C1组含量最高,C4组次之;各干预组血清CRP含量[c2组：（9.43±1.28） μg/L;C3组：（12.38±0.81） μg/L;C4组：（15.76±1.03） μg/L]、IL-6含量[C2组：（94.71±16.09） μg/L;C3组：（112.89±40.16） μg/L;C4组：（175.11±50.79） μg/L]在第2次干预后1周均达峰值,且均显著高于B组[CRP、IL-6含量分别为（6.96±1.30）、（43.36±7.46） μg/L]及C1组[CRP、IL-6含量分别为（8.41±0.46）、（73.59±27.89） μg/L]（P〈0.05）;之后出现不同程度下降,在最后的检测点各干预组中C2组血清CRP、IL-6含量最低（P〈0.01）.结论 伴As的CP大鼠,随牙周炎自然发展可能会引起血清炎症因子表达升高,进而加重As的病变程度;口腔干预治疗在短时间内可能会因全身炎症因子的急剧升高增加As的发生风险,但远期则可能会降低,且机械治疗组炎症因子降低最显著,血管改善也最明显.

Objective To explore the effect of variousoral interventions on the development of atherosclerosis in SD rats with chronic periodontitis and atherosclerosis.Methods Forty-four male SD rats were randomly divided into three groups,Group A（healthycontrol）,Group B（atherosclerosis,As） and Group C（chronic periodontitis with atherosclerosis,CP＋As）.Rats in Group C were further divided randomly into Subgroup Cl（natural process,n=7）,Subgroup C2（mechanical therapy,n=7）,Subgroup C3（systemic antibiotic treatment,n=7） and Subgroup C4（tooth extraction,n=7）.Rats in each subgroup of Group C received one of the appropriate oral interventions.The pathological lesions of carotid artery plaque were stained with hematoxylin and eosin（HE） and observed under a light microscope.The serum levels of C-reactive protein（CRP） and interleukin-6（IL-6） were detected by enzyme-linked immunosorbent assay （ELISA） in five different time points.Results Pathological results showed that increased foam cells and inflammatory cells were found in Group B.Irregular vessel wall,inflammatory cell,the foam cells,disordered elastic fibers were observed in Group C.While fewer in flammatory cells were found in Subgroup C2 than that in other subgroups.The changing trends of the serum levels of CRP and IL-6 were consistant with time went by.The levels of serum CRP,IL-6 in Groups B and C were significantly higher than that in Group A at all time points（P〈0.01）.The levels of serum CRP,IL-6 in Subgroup C1 became higher gradually（P〈0.05）with time being.The serum levels after oral interventions changed significantly compared with the baseline levels（P〈0.05）.One week after the second round of intervention,the serum levels of CRP（C2：[9.43 ± 1.28] μg/L,C3：[12.38±0.81] μg/L,C4：[15.76±1.03] μg/L） and IL-6 （C2：[94.71±16.09] μg/L,C3：[112.89± 40.16] μg/L,C4：[175.11 ±50.79] μg/L） in intervention subgroups reached the peaksand were significantly higher than that of Group B（CRP：[6.96±1.30] μg/L,IL-6：[43.36±7.46] μg/L） and Subgroup C 1（CRP：[8.41± 0.46] μg/L,IL-6：[73.59±27.89] μg/L）（P〈0.05）.The changes of serum levels then declined with time beingin each group/subgroupand level in Subgroup C2 was the lowest（P〈0.01）.Conclusions In chronic periodontitis of rats with atherosclerosis,permanent periodontitis mightsignificantly raise the risk of the development of atherosclerosis.Oral interventions increased the risk of atherosclerosis in a short period of time because of increased levels of serum inflammatory factors,but effective improvement could be observed on the As lesions after oral interventions in along term,especially after the periodontal mechanical therapy.