高压氧对载脂蛋白 E 基因敲除小鼠动脉粥样硬化的影响

Effect of hyperbaric oxygen on atherosclerosis in apoE-knockout mice

目的：通过对载脂蛋白E基因敲除（ apoE－／－）小鼠动脉粥样硬化（ AS）斑块病理形态学、血脂及相关炎症因子指标的观察，探讨高压氧对AS的作用和可能机制。方法28只8周龄雄性apoE－／－小鼠给予高脂饲料喂养8周，随机处死4只，取主动脉行苏木素伊红（ HE）染色，显微镜下观察确定建立小鼠动脉粥样硬化模型，剩余24只按数字表法随机分为高压氧组和对照组，每组各12只。高压氧组行高压氧处理，1次／d，共30 d，对照组不予以高压氧处理。高压氧治疗前、后测小鼠体质量。高压氧治疗结束当天处死小鼠，测定血脂及血清中CRP水平；进行主动脉HE染色，观察主动脉根部斑块的组织病理学特点，检测组织形态学相关指标，包括动脉斑块面积／管腔面积比值、内膜面积／中膜面积（ I／M）比值。结果高压氧治疗后，高压氧组小鼠血脂水平与对照组比较差异无统计学意义（ P＞0．05），但血清C反应蛋白（CRP）水平显著低于对照组（P＜0．05）。对照组小鼠主动脉可见大量AS斑块，内膜不规则增厚，且动脉斑块面积／管腔面积比值、I／M比值明显大于高压氧组小鼠（ P＜0．05）。结论高压氧有抑制AS的作用，其抑制AS作用独立于血脂之外；高压氧的抗炎作用可能是延缓AS发展原因之一。

Objective To study the effect of hyperbaric oxygen （ HBO） on the atherosclerosis （ AS） and the possible mechanism in apolipoprotein E （ apoE ）-knockout mice by observing the variation of atherosclerotic plaque pathological morphology , blood lipid and related inflammatory cytokines .Methods Twenty-eight 8-week old apoE-knockout male mice were fed with western-diet for 8 weeks.Four mice were randomly sacrificed to collect aortas for Hematoxylin and Eosin （ HE ） staining , and the AS model was ascertained under microscopy .Then, the remaining 24 mice were randomly assigned into the （ HBO） group （n=12） and the normal control group （n=12）.The animals in the HBO group were treated with HBO once a day for 30 days and the animals in the control group were left there without HBO treatment .The body mass of the mice were weighed both before and after termination of HBO treatment .The day after termination of HBO treatment, the mice were sacrificed for the detection of blood lipids and serum C-reactive protein （CRP）. Histopathological features of aorta were defined by Hematoxylin and Eosin （HE） staining.Subsequently, the area ratio of plaque and lumen and the ratio of intimal and media areas were analyzed by the image processing software.Results Following HBO treatment, there were no significant differences in blood lipid levels , when comparisons were made between the HBO group and the control group （P〉0.05）, however, the level of serum CRP in the HBO group was significantly lower than that of the control group （P〈0.05）.The HE staining indicated that large quantities of atherosclerotic plaques in the aorta of the control group and intima were thickened , and the area ratio of plaque and lumen and the ratio of intimal area and media area was obviously larger than those of the animals in the HBO group （ P 〈0.05）.Conclusions HBO could inhibit the development of atherosclerosis , which was not related to the modulation of blood lipid .The effect of HBO on anti-inflammation might be related to further progress of atherosclerosis .