目的探讨冠心病并发高血压患者外周血白细胞固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的表达与脂质代谢紊乱的关系。方法选取2017年6月~2018年5月在十堰市太和医院经冠脉造影确诊的196例冠心病患者,其...目的探讨冠心病并发高血压患者外周血白细胞固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的表达与脂质代谢紊乱的关系。方法选取2017年6月~2018年5月在十堰市太和医院经冠脉造影确诊的196例冠心病患者,其中冠心病并发高血压患者126例,单纯冠心病患者70例,同期选取健康对照者178例。收取外周血,测定相关生化代谢指标,实时荧光定量PCR检测外周血白细胞中SREBPs(SREBP-1,SREBP-2)的mRNA表达水平。分析SREBP-1 mRNA表达水平与生化代谢指标及高血压的相关性,采用多因素Logistic回归分析法探究冠心病并发高血压的独立风险因素。ROC曲线分析SREBP-1对于冠心病并发高血压危险程度的预测价值。结果单纯冠心病组及冠心病并发高血压组总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(Apo-A1)和载脂蛋白B(Apo-B)水平均低于对照组,差异具有统计学意义(均P<0.001)。相较于对照组及单纯冠心病组、冠心病并发高血压组SREBP-1 mRNA表达水平降低,差异有统计学意义(均P<0.05)。相关性分析显示SREBP-1与TC,HDL-C,LDL-C,Apo-A1,Apo-B呈正相关(r=0.207,0.216,0.121,0.246和0.114,均P<0.05)。将对照组及冠心病并发高血压组SREBP-1分别与各组的舒张压及收缩压做相关性分析,两组研究对象中SREBP-1与舒张压及收缩压均无相关性(均P>0.05)。多因素Logistic回归分析显示,校正年龄、性别、高脂血症及糖尿病之后,SREBP-1是冠心病并发高血压的独立风险因素,优势比(odds ratio,OR)=0.210,95%可信区间(confidence interval,CI)=0.079~0.561(P=0.002)。SREBP-1作为冠心病并发高血压危险因素,ROC曲线分析显示,曲线下面积(area under the cure,AUC)为0.580(0.503~0.657),敏感度和特异度分别为38.9%和77.0%(P=0.045)。结论SREBP-1表达水平在冠心病并发高血压患者外周血白细胞中显著降低,并与脂质代谢紊乱相关,可能�展开更多
Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism....Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.展开更多
固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)是调节胆固醇,脂肪酸和甘油三酯生物合成的主要转录因子,控制着脂肪生成和摄取等关键基因的表达。笔者总结了SREBPs的激活机制及其与胰岛素、环磷腺苷、肝脏X...固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)是调节胆固醇,脂肪酸和甘油三酯生物合成的主要转录因子,控制着脂肪生成和摄取等关键基因的表达。笔者总结了SREBPs的激活机制及其与胰岛素、环磷腺苷、肝脏X受体等相互作用,共同参与脂质代谢的过程,并结合最新研究动态对SREBPs的功能进行阐述。这些发现表明,抑制SREBPs可以成为治疗代谢性疾病的新策略,如Ⅱ型糖尿病,胰岛素抵抗,脂肪肝、动脉粥样硬化以及相关肿瘤等。展开更多
骨关节炎是影响人类健康的重要退行性疾病之一,造成了大量的身体残疾和医疗资源支出,但是该病的具体发病机制尚未阐明,从而无法治愈该病。编码固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的基因是近年来...骨关节炎是影响人类健康的重要退行性疾病之一,造成了大量的身体残疾和医疗资源支出,但是该病的具体发病机制尚未阐明,从而无法治愈该病。编码固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的基因是近年来研究较多的基因,在维持机体脂质代谢稳态中起到重要的作用,越来越多的研究证实,该基因与骨关节炎关系密切。该文将会从SREBPs基因介绍、SREBPs基因与骨关节炎的关系及其通过相关因子作用造成机体代谢障碍及骨关节炎的可能机制方面进行相关探讨,就SREBPs基因在骨关节炎中的作用作一综述,从而为相关研究提供便利。展开更多
文摘目的探讨冠心病并发高血压患者外周血白细胞固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的表达与脂质代谢紊乱的关系。方法选取2017年6月~2018年5月在十堰市太和医院经冠脉造影确诊的196例冠心病患者,其中冠心病并发高血压患者126例,单纯冠心病患者70例,同期选取健康对照者178例。收取外周血,测定相关生化代谢指标,实时荧光定量PCR检测外周血白细胞中SREBPs(SREBP-1,SREBP-2)的mRNA表达水平。分析SREBP-1 mRNA表达水平与生化代谢指标及高血压的相关性,采用多因素Logistic回归分析法探究冠心病并发高血压的独立风险因素。ROC曲线分析SREBP-1对于冠心病并发高血压危险程度的预测价值。结果单纯冠心病组及冠心病并发高血压组总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A1(Apo-A1)和载脂蛋白B(Apo-B)水平均低于对照组,差异具有统计学意义(均P<0.001)。相较于对照组及单纯冠心病组、冠心病并发高血压组SREBP-1 mRNA表达水平降低,差异有统计学意义(均P<0.05)。相关性分析显示SREBP-1与TC,HDL-C,LDL-C,Apo-A1,Apo-B呈正相关(r=0.207,0.216,0.121,0.246和0.114,均P<0.05)。将对照组及冠心病并发高血压组SREBP-1分别与各组的舒张压及收缩压做相关性分析,两组研究对象中SREBP-1与舒张压及收缩压均无相关性(均P>0.05)。多因素Logistic回归分析显示,校正年龄、性别、高脂血症及糖尿病之后,SREBP-1是冠心病并发高血压的独立风险因素,优势比(odds ratio,OR)=0.210,95%可信区间(confidence interval,CI)=0.079~0.561(P=0.002)。SREBP-1作为冠心病并发高血压危险因素,ROC曲线分析显示,曲线下面积(area under the cure,AUC)为0.580(0.503~0.657),敏感度和特异度分别为38.9%和77.0%(P=0.045)。结论SREBP-1表达水平在冠心病并发高血压患者外周血白细胞中显著降低,并与脂质代谢紊乱相关,可能�
基金Supported by The Natural Sciences and Engineering Research Council of Canada,No.NSERC 7594
文摘Plasma cholesterol level is determined by a complex dynamics that involves transport lipoproteins which levels are tightly dependent on how the liver and the intestine regulate cholesterol and biliary acid metabolism. Regulation of cholesterol and biliary acids by the liver and the intestine is in turn coupled to a large array of enzymes and transporters that largely influence the inflow and the outflow of cholesterol and biliary acids through these organs. The activity of the key regulators of cholesterol and biliary acids may be influenced by several external factors such as pharmacological drugs and the nutritional status. In recent years, more information has been gathered about the impact of estrogens on regulation of cholesterol in the body. Exposure to high levels of estrogens has been reported to promote cholesterol gallstone formation and women are twice as likely as men to develop cholesterol gallstones. The impact of estrogen withdrawal, such as experienced by menopausal women, is therefore of importance and more information on how the absence of estrogens influence cholesterol regulation is started to come out, especially through the use of animal models. An interesting alternative to metabolic deterioration due to estrogen deficiency is exercise training. The present review is intended to summarize the present information that links key regulators of cholesterol and biliary acid pathways in liver and intestine to the absence of estrogens in an animal model and to discuss the potential role of exercise training as an alternative.
文摘固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)是调节胆固醇,脂肪酸和甘油三酯生物合成的主要转录因子,控制着脂肪生成和摄取等关键基因的表达。笔者总结了SREBPs的激活机制及其与胰岛素、环磷腺苷、肝脏X受体等相互作用,共同参与脂质代谢的过程,并结合最新研究动态对SREBPs的功能进行阐述。这些发现表明,抑制SREBPs可以成为治疗代谢性疾病的新策略,如Ⅱ型糖尿病,胰岛素抵抗,脂肪肝、动脉粥样硬化以及相关肿瘤等。
基金the Research and Development Projects of Shenzhen,No.JCYJ20130402114702130the Program of Shenzhen Municipal Science and Technology Bureau,No.201302064~~
文摘骨关节炎是影响人类健康的重要退行性疾病之一,造成了大量的身体残疾和医疗资源支出,但是该病的具体发病机制尚未阐明,从而无法治愈该病。编码固醇调节元件结合蛋白(sterol regulatory element binding proteins,SREBPs)的基因是近年来研究较多的基因,在维持机体脂质代谢稳态中起到重要的作用,越来越多的研究证实,该基因与骨关节炎关系密切。该文将会从SREBPs基因介绍、SREBPs基因与骨关节炎的关系及其通过相关因子作用造成机体代谢障碍及骨关节炎的可能机制方面进行相关探讨,就SREBPs基因在骨关节炎中的作用作一综述,从而为相关研究提供便利。