Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway  

作　　者：TANG Jing-jing LI Guang-xi LIU Zhi-guo YI Rong YU Dong ZHANG Yue-bo ZHAO Shuang-qiao WANG Shi-han 

机构地区：[1]Department of Pneumology,Guang’anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing,100053,China [2]Department of Pulmonary and Critical Care Medicine,Mayo Clinic,Rochester,MN,55905,USA [3]Drug Clinical Trial Agency,Guang’anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing,100053,China [4]Department of Cardiovascular Medicine,Mayo Clinic,Rochester,MN,55905,USA [5]Department of Gynecology,Guang’anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing,100053,China [6]Department of Cardiovascular Medicine,Guang’anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing,100053,China

出　　处：《Chinese Journal of Integrative Medicine》2022年第6期509-517,共9页中国结合医学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China(No.81473465)。

摘　　要：Objective:To detect whether Danlou Tablet(DLT)regulates the hypoxia-induced factor(HIF)-1α-angiopoietin-like 4(Angptl4)mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia(CIH)-induced dyslipidemia and arteriosclerosis.Methods:The mature adipocytes were obtained from3 T3-L1 cell culturation and allocated into 8 groups including control groups(Groups 1 and 5,0.1 mL of cell culture grade water);DLT groups(Groups 2 and 6,0.1 mL of 1,000μg/mL DLT submicron powder solution);dimethyloxalylglycine(DMOG)groups(Groups 3 and 7,DMOG and 0.1 mL of cell culture grade water);DMOG plus DLT groups(Groups 4 and 8,DMOG and 0.1 mL of 1,000μg/mL DLT submicron powder solution).Groups1-4 used mature adipocytes and groups 5-8 used HIF-1α-siRNA lentivirus-transfected mature adipocytes.After 24-h treatment,real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1αand Angptl4.In animal experiments,the CIH model in ApoE^(-/-)mice was established.Sixteen mice were complete randomly divided into 4 groups including sham group,CIH model group[intermittent hypoxia and normal saline(2 mL/time)gavage once a day],Angptl4 Ab group[intermittent hypoxia and Angptl4 antibody(30 mg/kg)intraperitoneally injected every week],DLT group[intermittent hypoxia and DLT(250 mg/kg)once a day],4 mice in each group.After 4-week treatment,enzyme linked immunosorbent assay was used to detect the levels of serum total cholesterol(TC)and triglyceride(TG).Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques.Results:Angptl4 expression was dependent on HIF-1α,with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1α-transfected cells.DLT inhibited HIF-1αand Angptl4 mRNA expression(P<0.05 or P<0.01)and reduced HIF-1αand Angptl4 protein expressions with DMOG in mature adipocytes(all P<0.01),as the effect on HIF-1αprotein also existed in the pres

关 键 词：Danlou Tablet Chinese medicine hypoxia-induced factor angiopoietin-like 4 DYSLIPIDEMIA ARTERIOSCLEROSIS 

分 类 号：R285[医药卫生—中药学]