炎症诱发高血脂家兔产生抗动脉粥样硬化形成的预适应效应

The preconditioning effects induced by inflammation on hyperlipidemic rabbits against atherosclerosis

目的研究炎症感染及金黄色葡萄球菌(Staphyloccocus aureus,ST)疫苗模拟诱发高血脂家兔产生抗动脉粥样硬化形成的预适应效应。方法以高脂饲料喂饲家兔建立高血脂模型。两批家兔(感染处理与ST疫苗处理)各分为3组:正常对照组、模型组、炎症组或正常对照组、模型组、ST疫苗组。炎症组对感染溃疡性脚皮炎的家兔进行抗炎处理。ST疫苗组在给予高脂喂饲的同时,皮下注射ST疫苗乳剂(多点注射),2周1次,持续8周。3个月后测定其血脂水平、血浆黏度、主动脉上动脉粥样斑块面积、主动脉弓病理切片上的内膜/中膜比。对ST疫苗处理的家兔增加观察血清免疫球蛋白G(immunoglobulin,IgG)及相关炎症因子变化。结果两批家兔的模型组都呈高血脂水平,主动脉上粥样斑块连接成片,血浆黏度明显升高。炎症组和ST疫苗组家兔血脂虽呈不同程度降低,但仍保持在较高水平。炎症组家兔的斑块面积明显减少,内膜/中膜比较低;ST疫苗也可使其斑块面积明显减少,内膜/中膜比降低,但不如炎症组。炎症组血浆黏度有明显降低,但ST疫苗组略有升高。ST疫苗可使家兔血清IgG水平显著升高,使上升的致炎因子-肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)有所下降,并使抗炎因子-白细胞介素10(interleukin,IL-10)呈上升趋势。结论炎症感染可诱发高血脂家兔产生抗动脉粥样斑块形成的预适应效应,ST疫苗可一定程度模拟这一作用,但仍弱于炎症感染,显示两者对机体免疫动员存在一定差异,值得深入研究。

Objective To study the preconditioning effects induced by inflammation and simulated by Staphyloccocus aureus（ST） vaccine on hyperlipidemia rabbits against atherosclerosis. Methods The rabbit model of atherosclerosis was induced by atherogenic diet.Two batchs of rabbits were divided into three groups,respectively,i.e.control,model and inflammation or ST vaccine.Three months later,the animals were determined for some parameters,such as the serum lipid levels,plasma viscosity,atheros-clerotic plaque area on the aorta and their intima media ratio（with image analysis for the pathological slices）.The effects of ST vaccine on serum immunoglobulin（IgG） level and some cytokines related to the infection were detected as well. Results The hyperlipidemia levels were shown in both two model groups with large atherosclerotic plaque area on the aorta and enhanced plasma viscosity.The serum lipids were kept on the higher level in the groups of inflammation and ST vaccine though there was some kind of decrease.There was obviously less atherosclerotic plaque and small intima/media ratio on the aorta of infected rabbits.Such phenomenon was also shown in the rabbits with ST vaccine,but not as good as that in the infected rabbits.The plasma viscosity was decreased in the infected rabbits,while a bit increase was shown in the ST vaccine group.The serum IgG level was obviously enhanced by ST vaccine.The pro-inflammatory cytokine TNF-α was increased in model group and decreased by ST vaccine,and the anti-inflammatory cytokine IL-10 was increased by ST vaccine. Conclusions There was a kind of preconditioning effects induced by inflammation on hyperlipidemic rabbit against atherosclerosis.ST vaccine can imitate the effect in some extent,but it is weaker than that of inflammation.The different mechanism in mobilizing the internal immunity needs to be explored furtherly.