克拉霉素对C57BL/6J小鼠动脉粥样硬化及炎症反应的影响

目的观察肺炎衣原体（Chlamydia pneumoniae,Cpn）与动脉粥样硬化的关系以及克拉霉素的抗炎作用。方法 60只健康雄性C57BL/6J小鼠根据喂养的饲料及是否感染Cpn分为4组：对照组（n=6）、高脂组（n=6）、感染组（n=24）和感染＋高脂组（n=24）。Cpn感染组于试验开始每隔2周1次,共6次,分别经鼻内接种0.05ml Cpn（6.6×106IFU/ml）。对照组及高脂组以同样方法接种链球菌蛋白G（SPG）缓冲液。感染Cpn后（感染组、感染＋高脂组）依据有或无克拉霉素的治疗及治疗的时间进一步分为未治疗、早期及延迟治疗亚组。全自动生化分析仪检测小鼠的血脂,免疫荧光法检测Cpn IgG抗体。12周后处死小鼠,放免法测定IL-6、IL-8的水平,并取升主动脉大血管检测主动脉动脉粥样硬化的情况。结果高脂组的总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）明显高于对照组（P均〈0.01）。各组与对照组比较IL-6、IL-8的水平明显升高（P〈0.05或P〈0.01）;未治疗组高于早期及延迟治疗组（P〈0.01）,且延迟治疗组高于早期治疗组（P〈0.01）。与延迟治疗组比较,克拉霉素早期治疗组可以延缓动脉粥样硬化的发生。结论 Cpn协同高脂血症与动脉粥样硬化的形成密切相关。克拉霉素治疗能够减轻Cpn感染所致动脉粥样硬化的炎症反应。

The impact of clarithromycin on atherosclerosis and inflammatory reaction in C57BL/6J mice

Objective To observe the correlation between Chlamydia pneumoniae （Cpn） and atherosclerosis and anti-inflammatory effect of clarithromycin in C57BL/6J mice.Methods A total of 60 healthy male C57BL/6J mice were assigned to four groups based on feeding forage and whether infected by Cpn：control group（n=6）,high fat diet group（n=6）,infection group（n=24） and infection with high fat diet group（n=24）.The mice were infected by Cpn through intranasal vaccinating 0.05 ml Cpn（6.6×106 IFU/ml,once every 2 weeks,total six times）,and the SPG buffer was administrated in the same method in control group and high fat diet group.Meanwhile,the mice in infection group and infection with high fat diet group were further redivided into three subgroups：non-treatment group,early treatment group and delayed treatment group based on with or without clarithromycin therapy and therapeutic time.The blood lipid was assayed by auto-biochemical analyzer,and the Cpn IgG antibody was measureded by immunofluorescence.The levels of IL-6,IL-8 were detected by radioimmunity method,and the condition of atherosclerosis was detected by pathology of vessels of aortic artery after the mice were killed in 12 weeks. Results Compared with control group,the levels of TC,TG and LDL-C significantly elevated in high fat diet group （all P0.01）,and the levels of IL-6 and IL-8 significantly elevated in the other groups （P0.05 or P0.01）.The levels of IL-6 and IL-8 were higher in non-treatment group than those in early and delayed treatment groups（all P0.01）,and the latter were higher than those in the former （P0.01）.Compared with the delayed treatment group,the occurrence of atherosclerosis could be obviously delayed in the early treatment group.Conclusions Cpn infection and high blood lipid correlate closely with athrosclerosis.Early or delayed therapy of clarithromycin can decrease inflammatory reaction of atherosclerosis caused by Cpn infection in C57BL/6J mice.