有氧运动对ApoE^(-/-)小鼠生物钟基因Cry1表达的影响及其抗动脉粥样硬化机制

Effect of aerobic exercise on the expression of Cry1 in ApoE^(-/-)mice and its anti-atherosclerotic mechanism

目的观察有氧运动对ApoE^(-/-)小鼠主动脉生物钟基因Cry1表达的影响并探讨其发挥抗动脉粥样硬化作用的机制。方法研究实施时间:2022年3月至2022年11月。22只8周龄雄性ApoE^(-/-)小鼠随机分成模型组(11只)和运动组(11只),运动组进行12周的跑台运动,每2周对小鼠称重并记录体质量变化情况。比色法测定血清中三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的浓度;酶联免疫吸附试验(ELISA)检测血清中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α的浓度;组织化学染色法观察主动脉组织斑块形成及脂质沉积程度;real-time PCR和免疫组织化学染色检测主动脉管壁Cry1基因表达情况。采用独立样本t检验或单因素方差分析。结果与模型组相比,运动组小鼠的体质量降低(P<0.01),血清LDL-C、TC、TG、IL-1β、IL-6、TNF-α含量下降(均P<0.01),HDL-C含量升高(P<0.01),主动脉斑块面积及脂质沉积情况减轻(均P<0.01),主动脉组织中Cry1基因mRNA和蛋白表达水平升高(均P<0.01)。结论有氧运动可以提高ApoE^(-/-)小鼠主动脉管壁生物钟基因Cry1的表达水平,降低血脂及相关炎性因子的浓度,并抑制动脉粥样硬化斑块的形成,提示有氧运动的抗动脉粥样硬化作用可能与其上调小鼠主动脉血管壁生物钟基因Cry1的表达有关。

Objective To observe the effect of aerobic exercise on the expression of aortic clock gene Cry1 in ApoE^(-/-)mice and explore the mechanism of its anti-atherosclerotic effect.Methods The study was conducted from March 2022 to November 2022.Twenty-two 8-week-old male ApoE^(-/-)mice on a high-fat diet were randomly divided into two groups:an exercise group(n=11)and a model group(n=11).The exercise group did treadmill running for 12 weeks.Weight changes of all ApoE^(-/-)mice were monitored regularly(every 2 weeks).The serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were determined by colorimetric method.The serum levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-αwere detected by enzyme-linked immunosorbent assay(ELISA).The degrees of aortic plaque formation and lipid deposition were observed by histochemical staining.The expression of Cry1 gene in the aorta was detected by real-time PCR and immunohistochemical staining.Independent sample t test or one-way analysis of variance were used.Results Compared with those in the model group,the body mass of the mice in the exercise group was decreased(P<0.01),the contents of LDL-C,TC,TG,IL-1β,IL-6,and TNF-αin serum were decreased(all P<0.01),the content of HDL-C was increased(P<0.01),the aortic plaque area and lipid deposition were decreased(all P<0.01),and the mRNA and protein expression levels of Cry1 gene were increased in the aorta(all P<0.01).Conclusion Aerobic exercise increases the expression level of Cry1 in the aorta of ApoE^(-/-)mice,decreases the levels of serum lipids and inflammatory cytokines,and reduces the formation of atherosclerosis plaques,which suggests that the anti-atherosclerotic effect of aerobic exercise may be related to the up-regulation of Cry1 expression in the aortic wall.