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.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Oct 7;52(5):627-635. doi: 10.3724/zdxbyxb-2023-0164.
To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats.
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 high-fat 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), low-density 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.
Compared with the normal control group, the white fat weight (<0.01), white fat coefficient (<0.05) and Lee's coefficient (<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 (<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 (<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 <0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all <0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all <0.05).
Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.
探讨降脂合剂调节肥胖大鼠糖脂代谢的作用机制。
30 只健康雄性 SD 大鼠随机分为正常对照组、模型对照组和降脂合剂治疗组，每组 10 只。正常对照组给予普通饲料喂养，模型对照组和降脂合剂治疗组给予高脂饲料诱导肥胖模型，治疗组给予降脂合剂 50 g/kg 灌胃。干预 8 周后，检测 3 组大鼠血糖（GLU）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）水平。采用定量逆转录 PCR 检测各组大鼠白色和棕色脂肪组织中 PR 结构域包含 16（PRDM16）和解偶联蛋白 1（UCP1）的表达水平；采用 Western blot 检测大鼠白色和棕色脂肪组织中 PRDM16 的表达，以及白色脂肪组织中 Toll 样受体 4（TLR4）、核因子-κB（NF-κB）和 NF-κB 抑制因子α（IκBα）的表达；采用免疫组织化学法检测白色和棕色脂肪组织中 UCP1 蛋白的表达。
与正常对照组相比，模型对照组大鼠白色脂肪重量（P<0.01）、白色脂肪系数（P<0.05）和 Lee 指数（P<0.01）均显著增加；GLU、TC、TG 和 LDL-C 含量均升高，TG 含量升高更明显（P<0.05）。模型对照组大鼠白色和棕色脂肪组织中 PRDM16 和 UCP1 的 mRNA 和蛋白表达水平均显著降低（P<0.05）。与模型对照组相比，降脂合剂治疗组大鼠白色脂肪重量和白色脂肪系数及 Lee 指数均显著降低（均 P<0.01），GLU、TC、TG 和 LDL-C 水平均降低，TG 含量降低更明显（P<0.01）；棕色和白色脂肪组织中 PRDM16 和 UCP1 的 mRNA 和蛋白表达水平均升高。与正常对照组相比，模型对照组大鼠白色脂肪组织中 TLR4、磷酸化 IκBα 和 NF-κB-p65 蛋白的表达水平均显著升高（均 P<0.01），而治疗组上述蛋白的表达水平均显著低于模型对照组（均 P<0.05）。
降脂合剂通过调节 TLR4/IκBα/NF-κB 信号通路，可减轻高脂饮食引起的大鼠体脂增加，改善生化指标异常，并促进白色和棕色脂肪组织中 UCP1 和 PRDM16 等关键蛋白的表达。
