非酒精性脂肪性肝炎小鼠肝组织中脂蛋白脂肪酶及其相关调控因子的表达及二乙基二硫代氨基甲酸对其的调控作用  

Expression of lipoprotein lipase and its related regulatory factors in the liver of mice with non-alcoholic steatohepatitis and its regulation by diethyldithiocarbamate

作　　者：康碧莲 孙祥云 于庆红 刘琳[1] 丛敏[1] 王萍[1] 刘天会[1] KANG Bi-lian;SUN Xiang-yun;YU Qing-hong(Liver Research Center,Beijing Friendship Hospital,Capital Medical University,Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis,National Clinical Research Center of Digestive Diseases,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院肝病中心肝硬化转化医学北京市重点实验室暨国家消化系统疾病临床医学研究中心,北京100050

出　　处：《临床和实验医学杂志》2023年第8期785-788,共4页Journal of Clinical and Experimental Medicine

基　　金：国家自然科学基金(编号:82070618;81770596)。

摘　　要：目的探讨脂蛋白脂肪酶(LPL)及其相关调控因子在非酒精性脂肪性肝炎(NASH)小鼠肝组织中的变化和二乙基二硫代氨基甲酸(DDC)对其的调控作用。方法将15只雄性C57BL/6小鼠按照随机数字表法分为3组,每组5只。对照组给予普通饲料喂养;模型组给予胆碱缺乏的氨基酸(CDAA)饲料喂养,建立NASH模型;治疗组在采用高脂CDAA饲料喂养的同时给予DDC灌胃治疗。用Real-time PCR方法检测NASH小鼠肝组织中LPL及其活性相关调节因子的表达变化;探讨DDC对LPL及其活性相关调节因子的调控作用。结果模型组小鼠肝组织中LPL基因表达为3.527±1.389,显著高于对照组(1.233±0.887),LPL酶活性的负性调控因子血管生成素样蛋白ANGPTL3、ANGPTL4及载脂蛋白apoC-Ⅰ、apoC-Ⅲ的表达分别为0.060±0.045、0.396±0.203、0.292±0.159、0.145±0.058,均显著低于对照组(1.126±0.650、1.051±0.373、1.016±0.205、1.141±0.751),差异均有统计学意义(P<0.05)。治疗组小鼠肝组织中LPL基因表达为0.597±0.111,显著低于模型组(1.030±0.288),ANGPTL3、ANGPTL4、apoC-Ⅰ表达分别为1.284±0.181、2.040±0.602、1.514±0.369,均显著高于模型组(1.006±0.119、0.909±0.088、0.969±0.124),差异均有统计学意义(P<0.05)。结论NASH小鼠肝组织中LPL表达升高,LPL酶活性抑制因子表达降低;DDC抑制LPL基因表达,并上调LPL酶活性的负性调控因子。Objective To investigate the expression of lipoprotein lipase(LPL)and its related regulators in mice liver tissues with non-alcoholic steatohepatitis(NASH)and its regulation by diethyldithiocarbamate(DDC).Methods Fifteen male C57BL/6 mice were divided into three groups with 5 mice in each group.The control group was fed with normal diet,the model group was fed with choline deficient amino acid-defined diet(CDAA)to establish model of NASH,and the treatment group underwent DDC gavage while feeding with high-fat CDAA feed.Real-time PCR was used to analyze the expression of LPL and LPL activity-related regulatory genes in the liver tissues of NASH mice.The role of DDC in the regulation of LPL and LPL activity-related regulatory genes was explored.Results The expression of LPL gene in the liver tissue of mice in model group was 3.527±1.389,which was significantly higher than that of the control group(1.233±0.887),and the expression of negative regulators of LPL enzyme activity,ANGPTL3,ANGPTL4,apoC-Ⅰand apoC-Ⅲwere significantly decreased in the model group with values of 0.060±0.045,0.396±0.203,0.292±0.159,and 0.145±0.058,respectively,as compared to the control group with values of 1.126±0.650,1.051±0.373,1.016±0.205,and 1.141±0.751,the differences were statistically significant(P<0.05).The expression of LPL gene in the liver tissue of mice in the treatment group was 0.597±0.111,which was significantly lower than that in the model group(1.030±0.288),and the expression of ANGPTL3,ANGPTL4,and apoC-Ⅰwere 1.284±0.181,2.040±0.602,1.514±0.369,which were significantly higher than those in the model group(1.006±0.119,0.909±0.088,0.969±0.124),the differences were statistically significant(P<0.05).Conclusion The expression of LPL is increased and the expressions of negative regulators of LPL activity are decreased in liver tissues of NASH mice.DDC inhibits the expression of LPL and up-regulates the negative regulators of LPL activity.

关 键 词：小鼠 脂蛋白脂肪酶 非酒精性脂肪性肝炎 二乙基二硫代氨基甲酸 

分 类 号：R575.5[医药卫生—消化系统]