代综方对肥胖小鼠白色脂肪组织糖原代谢的影响  

Effects of Daizong Prescription on Glycogen Metabolism in White Adipose Tissue of Obese Mice

作　　者：张莉唯 刘喜明[1] 付守强 冯慧 汤阳 徐婧 朱晓云[1] ZHANG Liwei;LIU Ximing;FU Shouqiang;FENG Hui;TANG Yang;XU Jing;ZHU Xiaoyun(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Beijing University of Chinese Medicine,Beijing 100029,China;Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]北京中医药大学,北京100029 [3]南京中医药大学,江苏南京210023

出　　处：《中国中医药信息杂志》2024年第2期90-96,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：北京市自然科学基金(7232309);国家自然科学基金青年基金(81804085)。

摘　　要：目的观察代综方对肥胖小鼠脂肪组织糖原代谢的影响,探讨其激活白色脂肪组织棕色化的调控机制。方法采用高脂饲料喂养C57BL/6J小鼠建立肥胖模型,将成模小鼠分为模型组、二甲双胍组(0.15 g/kg)和代综方低(0.20 g/kg)、高(0.40 g/kg)剂量组,另取常规维持饲料喂养的小鼠作为正常组,每组12只,各给药组分别予相应药物灌胃,连续6周。测量小鼠体质量及空腹血糖,检测血清三酰甘油(TG)、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)含量,取肩胛棕色脂肪组织及腹股沟、肾周、附睾白色脂肪组织,分别测定脂肪组织质量并计算体脂系数,HE染色观察脂肪组织形态变化,PAS染色观察脂肪组织糖原分布,免疫组化染色检测腹股沟白色脂肪组织糖原合成酶2(Gys2)、蛋白磷酸酶1调节亚基3c(Ppp1r3c)、糖原合酶激酶(GSK)-3β表达。结果与正常组比较,模型组小鼠各时点体质量和空腹血糖均显著升高(P<0.05,P<0.01),血清TC、HDL-C含量显著升高(P<0.01);腹股沟、肾周、附睾白色脂肪组织质量及体脂系数显著升高(P<0.01),腹股沟白色脂肪组织细胞肥大、呈大空泡样,糖原积累较少,Gys2、Ppp1r3c表达显著降低(P<0.01)。与模型组比较,代综方高剂量组小鼠给药4、6周体质量和空腹血糖均显著降低(P<0.05,P<0.01),血清TG、TC、HDL-C、LDL-C含量均显著降低(P<0.01);肾周、附睾白色脂肪组织质量及体脂系数显著降低(P<0.05,P<0.01),腹股沟白色脂肪组织质量显著降低(P<0.05),腹股沟白色脂肪组织可见多处形态不规则的小空泡,周围伴有细胞核聚集,糖原积累增加,Gys2、Ppp1r3c阳性表达显著升高(P<0.01)。各组小鼠腹股沟白色脂肪组织GSK-3β表达差异无统计学意义。结论代综方可通过上调Ppp1r3c表达提高Gys2活性,促进糖原合成,诱导脂肪组织棕色化,增加脂肪产热,改善肥胖及相关糖脂代谢紊乱。Objective To observe the effects of Daizong Prescription on glycogen metabolism in adipose tissue of obese mice;To explore its regulatory mechanism in activating browning in the white adipose tissue.Methods A obesity model was established by feeding high-fat diet to C57BL/6J mice.The obese mice were divided into model group,metformin group(0.15 g/kg),and Daizong Prescription low-(0.20 g/kg)and high-dosage(0.40 g/kg)groups.Mice fed a standard diet were set as the normal group,with 12 mice in each group.Each medication group was given corresponding drugs by gavage for 6 consecutive weeks.Body mass and fasting blood glucose were monitored,serum triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)contents were measured.Brown adipose tissue from the interscapular region and white adipose tissue from the inguinal,perirenal and epididymal region were collected,the adipose tissue mass was measured,and the body fat coefficient was calculated.HE staining was performed to observe morphological changes in adipose tissue,PAS staining was used to observe glycogen distribution in adipose tissue,immunohistochemistry staining was performed to detect the expressions of Gys2,Ppp1r3c,and GSK-3βin inguinal white adipose tissue.Results Compared with the normal group,the body mass and fasting blood glucose in different time points of the model group significant increase(P<0.05,P<0.01),and serum TC and HDL-C contents significantly increased(P<0.01);the mass and body fat coefficient of white adipose tissue in inguinal,perirenal,and epididymis significantly increased(P<0.01),the cells in white adipose tissue in inguinal were hypertrophic and appeared as large vacuoles,with less glycogen accumulation,the expressions of Gys2 and Ppp1r3c significantly decreased(P<0.01).Compared with the model group,the mice in Daizong Prescription high-dosage group showed a significant decrease in body mass and fasting blood glucose at 4 and 6 weeks of administration(P<0.05,P<0.01

关 键 词：肥胖 代综方 脂肪组织 糖原合成 小鼠 

分 类 号：R285.5[医药卫生—中药学]