降浊合剂通过调节TLR4/IκBα/NF-κB信号通路影响肥胖大鼠糖脂代谢  

Chinese medicine Jiangzhuo mixture regulates glucose and lipid metabolism in obese rats through TLR4/IκBα/NF-κB signaling pathway

作　　者：苏琼 江丹娜 钟钊 周开 龚文波 SU Qiong;JIANG Danna;ZHONG Zhao;ZHOU Kai;GONG Wenbo(Department of Endocrinology,Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University,Ningbo 315010,China;Department of Cardiology,Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University,Ningbo 315010,China;Department of Rheumatology,Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University,Ningbo 315010,China)

机构地区：[1]浙江中医药大学附属宁波中医院内分泌科,浙江宁波315010 [2]浙江中医药大学附属宁波中医院心内科,浙江宁波315010 [3]浙江中医药大学附属宁波中医院风湿科,浙江宁波315010

出　　处：《浙江大学学报（医学版）》2023年第5期627-635,共9页Journal of Zhejiang University(Medical Sciences)

基　　金：宁波市科技计划(2019A610359);宁波市医疗卫生品牌学科建设项目(PPXK2018-07)

摘　　要：目的:探究降浊合剂影响肥胖大鼠糖脂代谢的机制。方法:30只健康雄性SD大鼠随机分为正常对照组、模型对照组、降浊合剂组,每组各10只,其中正常对照组给予普通饲料喂养,模型对照组给予高脂饲料喂养,降浊合剂组在给予高脂饲料喂养的同时给予50 g/kg降浊合剂浓缩液灌胃。各组干预8周后,采用全自动生化分析仪检测各组大鼠血糖、总胆固醇、三酰甘油、低密度脂蛋白胆固醇(LDLC)和高密度脂蛋白胆固醇(HDL-C)水平;采用定量逆转录PCR法检测各组大鼠白色、棕色脂肪中PR结构域蛋白16(PRDM16)、解偶联蛋白1(UCP1)信使RNA表达;采用蛋白质印迹法检测各组大鼠白色、棕色脂肪中PRDM16以及各组大鼠白色脂肪中Toll样受体4(TLR4)、磷酸化核因子抑制蛋白(IκBα)和核因子κB(NF-κB)蛋白表达水平;采用免疫组织化学法检测各组大鼠白色、棕色脂肪中UCP1蛋白表达水平。结果:与正常对照组比较,模型对照组白色脂肪质量(P<0.01)、白色脂肪系数(P<0.05)和Lee’s系数(P<0.01)均显著升高;血糖、总胆固醇、三酰甘油、LDL-C含量均升高,其中三酰甘油含量升高明显(P<0.05);白色脂肪和棕色脂肪PRDM16、UCP1的信使RNA和蛋白表达水平均明显降低(均P<0.05)。与模型对照组比较,降浊合剂组的白色脂肪质量、白色脂肪系数和Lee’s系数均明显降低(均P<0.01);血糖、总胆固醇、三酰甘油、LDL-C含量均有所降低,其中三酰甘油含量明显降低(P<0.01);棕色脂肪和白色脂肪中PRDM16、UCP1的信使RNA和蛋白的表达水平上升。此外,与正常对照组比较,模型对照组白色脂肪中TLR4、磷酸化IκBα和NF-κB-p65蛋白表达水平明显升高(P<0.01),而降浊合剂组上述蛋白的表达水平相对于模型对照组显著下降(均P<0.05)。结论:降浊合剂可以通过调节SD大鼠体内TLR4/IκBα/NF-κB信号通路缓解高脂饮食诱导的体脂增加、生化指标异常表达及促进关键�Objective:To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats.Methods:Thirty healthy male SD rats were randomly divided into normal control group,model control group,and Jiangzhuo mixture treatment group,with 10 rats in each group.The rats in the normal control group were fed with normal diet,the obesity model was induced by feeding highfat diet in the model control group and the Jiangzhuo mixture treatment group,the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage.After 8 weeks of intervention,the blood glucose(GLU),total cholesterol(TC),triglyceride(TG),lowdensity lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)levels were measured in the three groups.Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16(PRDM16)and uncoupling protein 1(UCP1)in white and brown adipose tissues of the rats in each group;Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats,and Toll-like receptor 4(TLR4),nuclear factor-κB(NF-κB)and inhibitor of NF-κB alpha(IκBα)in the white adipose tissue;immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues.Results:Compared with the normal control group,the white fat weight(P<0.01),white fat coefficient(P<0.05)and Lee’s coefficient(P<0.01)were significantly increased in the model control group;the contents of GLU,TC,TG and LDL-C were all increased,and the content of TG was significantly increased(P<0.05)in the model control group.The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased(P<0.05)in the model control group.Compared with the model control group,the white fat weight and white fat coefficient and Lee’s coefficient were significantly reduced in the Jiangzhuo mixture treatment group(all P<0.01),the levels of GLU,TC,TG,and LDL-C in the the treatme

关 键 词：降浊合剂 肥胖 脂代谢 糖代谢 PR结构域蛋白16 解偶联蛋白1 SD大鼠 

分 类 号：R966[医药卫生—药理学]