LXR及其靶基因COX-2和CETP在肥胖OSAHS幼鼠肝组织中的保护作用  

The protective effects of LXR and its target genes COX-2 and CETP on liver tissues of young obese OSAHS rats

作　　者：赖明昱 叶新华[2] LAI Mingyu;YE Xinhua(The First Clinical Medicine College of Lanzhou University,Lanzhou 730000;Department of Pediatrics,The First Hospital of Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学第一临床医学院,甘肃兰州730000 [2]兰州大学第一医院儿科,甘肃兰州730000

出　　处：《西安交通大学学报（医学版）》2024年第6期895-901,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：甘肃省自然科学基金资助项目(No.20JR10RA695)。

摘　　要：目的阐明肝X受体(liver X receptor,LXR)及其靶基因环氧化酶-2(cyclooxygenase-2,COX-2)、胆固醇酯转移蛋白(cholesteryl ester transfer protein,CETP)的高表达是肥胖幼鼠阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)发病过程中的保护性因素,为肥胖儿童OSAHS的发病机制提供基础研究资料。方法24只3~4周龄雄性Wistar幼鼠分为正常对照组(control组)、单纯肥胖组(obesity组)、单纯OSAHS组(OSAHS组)、肥胖+OSAHS组(obesity+OSAHS组)。HE染色观察幼鼠肝组织病理变化;蛋白免疫印迹法(Western blotting)检测幼鼠肝组织中LXRα、COX-2、CETP的表达水平;运用免疫组化方法检测幼鼠肝组织中LXRα、COX-2、CETP的表达水平及分布情况。结果单纯肥胖组和肥胖+OSAHS组幼鼠体质量、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)含量与正常对照组相比均明显增加(P<0.05),单纯OSAHS组和肥胖+OSAHS组幼鼠血氧饱和度与正常对照组相比均明显降低(P<0.05)。单纯肥胖组、单纯OSAHS组及肥胖+OSAHS组肝组织与正常对照组肝组织相比均有明显损伤,肥胖+OSAHS组肝组织损伤较单纯肥胖组、单纯OSAHS组肝组织损伤程度明显升高。单纯OSAHS组和单纯肥胖组幼鼠肝组织中LXRα、COX-2、CETP表达水平较正常对照组均明显升高(P<0.05)。肥胖+OSAHS组幼鼠肝组织中LXRα、COX-2、CETP表达水平较其余各组均明显升高(P<0.05)。结论LXR及其靶基因COX-2、CETP在肥胖OSAHS幼鼠肝脏中高表达,是发病过程中的可能保护性因素。Objective To illuminate that the high expressions of liver X receptor(LXR),cyclooxygenase-2(COX-2),and cholesteryl ester transfer protein(CETP)are protective factors in the pathogenesis of obesity and obstructive sleep apnea-hypopnea syndrome(OSAHS),in order to provide basic information for the prevention and treatment of obesity in children with OSAHS.Methods A total of 24 young rats aged 3-4 weeks were randomly divided into normal control group,obesity group,OSAHS group,and obesity and OSAHS group.We used hematoxylin-eosin(HE)staining to observe the histopathological changes in the liver of the young rats,Western blotting and immunohistochemistry to test the expression levels and distribution of LXRα,COX-2,and CETP in liver tissues of the rats.Results The body weight,total cholesterol(TC),and triglyceride(TG)content of the rats in obesity group and obesity+OSAHS group were significantly increased compared with that in the control group(P<0.05),and the oxygen saturation of the rats in OSAHS group and obesity+OSAHS group was significantly decreased compared with that in the control group(P<0.05).The liver tissue had significant damage in obesity group,OSAHS group and obesity+OSAHS group compared with that in the normal control group,and obesity+OSAHS group had the most severe liver tissue damage.The expression levels of LXRα,COX-2,and CETP were significantly higher in the liver tissues of young rats in OSAHS group and obesity group compared with those in the normal control group(P<0.05).The expression levels of LXRα,COX-2,and CETP were significantly higher in the liver tissues of young rats in obesity+OSAHS group compared with those in the other groups(P<0.05).Conclusion LXR and its target genes COX-2 and CETP are highly expressed in the liver tissues of obese OSAHS rats and are possible protective factors in the pathogenesis of obesity and OSAHS.

关 键 词：肝X受体(LXR) 阻塞性睡眠呼吸暂停综合征(OSAHS) 肥胖 幼鼠 保护作用 

分 类 号：R56[医药卫生—呼吸系统]