克拉霉素对C57BL/6J小鼠动脉粥样硬化及炎症反应的影响

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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。 Objective To observe the relationship between Chlamydia pneumoniae (Cpn) and atherosclerosis and the anti-inflammatory effect of clarithromycin. Methods Sixty healthy male C57BL / 6J mice were divided into 4 groups according to their diet and Cpn infection: control group (n = 6), high fat group (n = 6), infection group (n = 24) High-fat group (n = 24). The Cpn infection group was given once every 2 weeks for 6 times at the beginning of the experiment, and intranasally inoculated with 0.05 ml Cpn (6.6 × 10 6 IFN / ml). Control and hyperlipidemic groups were similarly challenged with streptococcal protein G (SPG) buffer. Infection with Cpn (infection group, infection + hyperlipidemia group) was further divided into untreated, early and delayed treatment subgroups based on the time of treatment and treatment with or without clarithromycin. Blood lipid was detected by automatic biochemical analyzer and Cpn IgG antibody was detected by immunofluorescence. After 12 weeks, the mice were sacrificed and the levels of IL-6 and IL-8 were determined by radioimmunoassay. Atherosclerotic plaques in the ascending aorta were detected. Results The levels of total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) in hyperlipidemic group were significantly higher than those in control group (all P <0.01). The levels of IL-6 and IL-8 in each group were significantly higher than those in the control group (P <0.05 or P <0.01), those in the untreated group were higher than those in the early and delayed groups (P <0.01) Early treatment group (P <0.01). Compared with the delayed treatment group, clarithromycin early treatment group can delay the occurrence of atherosclerosis. Conclusions Cpn synergistic hyperlipidemia is closely related to the formation of atherosclerosis. Clarithromycin treatment attenuated the atherosclerotic inflammatory response induced by Cpn infection.
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