雌激素缺乏对大鼠肝脏胆固醇代谢的影响及机制  

Effect and mechanism of estrogens deficiency on cholesterol metabolism in rat liver

作　　者：李松涛[1] 李然[2] 李琳[1] 宁华[1] 郭福川[1] 孟凡玉[1] 吕琳[1] 

机构地区：[1]哈尔滨医科大学公共卫生学院营养与食品卫生学教研室,150086 [2]哈尔滨市疾病预防控制中心,150086

出　　处：《实用医学杂志》2015年第21期3489-3492,共4页The Journal of Practical Medicine

基　　金：黑龙江省教育厅科学技术研究(面上)项目(编号:12531334)

摘　　要：目的:女性绝经后胆固醇水平升高是诱发心血管疾病的重要风险因素,然而雌激素缺乏如何影响胆固醇代谢及分子机制尚未完全明确。本研究通过卵巢切除术模拟女性雌激素缺乏状态,并对调节肝脏胆固醇代谢的基因进行检测以明确分子机制。方法:试验采用8周龄Wistar大鼠,分别于卵巢去除后1、4、8周,检测血清胆固醇、粪便胆固醇等指标,应用荧光定量PCR检测肝脏胆固醇代谢相关基因的m RNA水平。结果:与假手术组相比,卵巢去除组大鼠血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平显著上升。PCR结果显示,胆固醇分解关键酶胆固醇7α-羟化酶(CYP7A1)的m RNA水平显著下降(P<0.05),其负向调节转录因子小异二聚体伴侣(SHP)的m RNA水平显著升高(P<0.05)。结论:雌激素缺乏状态下,肝脏胆固醇分解代谢受到抑制可能是导致循环胆固醇水平上升的主要原因,其中SHP抑制的CYP7A1水平的显著降低是其主要分子机制。Objective Elevated level of cholesterol is a critical risk factor for cardiovascular diseases in postrnenopausal women. However, the potential mechanisms underlying estrogen deficiency-induced abnormal metabolism in hepatic cholesterol are still unclear. This study aimed to investigate the expressions of key genes participating in cholesterol metabolism via employing ovariectomized rat to mimic postmenopausal status. Methods Wistar rats （8-week of age） were randomly divided into the sham-operated group and the ovariectomized group. After 1-, 4-, 8-week feeding, levels of serum cholesterol, fecal cholesterol and other indicators were determined. The mRNA level of cholesterol metabolism-related genes in rat liver were determined by fluo- rescent quantitative PCR. Results Serum levels of trig]ycerides, total cholesterol, and low-density lipoprotein cholesterol were significantly increased in the ovarlectomized group compared with the sham-operated group. Cholesterol 7 alpha-hydroxylase （CYPTA1） was significantly reduced at mRNA level in the ovariectomized group （P 〈 0.05）, meanwhile, the mRNA expression of its negative transcriptional regulator small heterodimer partner （SHP） was dramatically up-regulated （P 〈 0.05）. Conclusions The decreased cholesterol catabolism is proba- bly the main reason for the increased level of serum cholesterol in estrogens deficiency rat. SHP is mechanistical- ly involved in this physiological process.

关 键 词：卵巢去除 胆固醇 代谢 机制 

分 类 号：R54[医药卫生—心血管疾病]