Objective:To detect whether Danlou Tablet(DLT)regulates the hypoxia-induced factor(HIF)-1 α-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 from 3T3-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 1,000 μg/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 1,000 μg/mL DLT submicron powder solution).Groups 1-4 used mature adipocytes and groups 5-8 used HIF-1 α-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-1 α and 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-1 α,with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α-transfected cells.DLT inhibited HIF-1 α and Angptl4 mRNA expression(P＜0.05 or P＜0.01)and reduced HIF-1 α and Angptl4 protein expressions with DMOG in mature adipocytes(all P＜0.01),as the effect on HIF-1 α protein also existed in the presence of siHIF-1 α(P＜0.01).ApoE-/-mice treated with CIH had increased TG and TC levels(all P＜0.01)and atherosclerotic plaque.Angptl4 antibody and DLT both reduced TG and TC levels(all P＜0.01),as well as reducing atherosclerotic plaque areas,narrowing arterial wall thickness and alleviating atherosclerotic lesion symptoms to some extent.Conclusion:DLT had positive effects in improving dyslipidemia and arteriosclerosis by inhibiting Angptl4 protein level through HIF-1 α-Angptl4 mRNA signaling pathway.

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

Department of Pneumology,Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing(100053),China;Department of Pulmonary and Critical Care Medicine,Mayo Clinic,Rochester,MN 55905,United States;Drug Clinical Trial Agency,Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing(100053),China;Department of Cardiovascular Medicine,Mayo Clinic,Rochester,MN 55905,United States;Department of Gynecology,Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing(100053),China;Department of Cardiovascular Medicine,Guang'anmen Hospital,Chinese Academy of Chinese Medical Sciences,Beijing(100053),China

中国结合医学杂志（英文版）

[1]TANG Jing-jing;LI Guang-xi;LIU Zhi-guo;YI Rong;YU Dong;ZHANG Yue-bo;ZHAO Shuang-qiao;WANG Shi-han-.Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1 α-Angptl4 mRNA Signaling Pathway)[J].中国结合医学杂志（英文版）,2022(06):509-517

Danlou,Arteriosclerosis,culturation,dimethyloxalylglycine

Tablet,Improves,Chronic,Intermittent,Hypoxia,Induced,Dyslipidemia,by,Angptl4,Signaling,Pathway,Objective,To,detect,whether,DLT,regulates,hypoxia,induced,angiopoietin,like,signaling,pathway,explore,role,treating,chronic,intermittent,CIH,dyslipidemia,arteriosclerosis,Methods,mature,adipocytes,were,obtained,from,3T3,L1,allocated,into,groups,including,control,Groups,culture,grade,water,submicron,powder,solution,DMOG,plus,used,siRNA,lentivirus,transfected,After,treatment,real,polymerase,chain,reaction,blot,employed,determine,protein,levels,animal,experiments,model,ApoE,mice,was,established,Sixteen,complete,randomly,divided,sham,normal,saline,gavage,once,day,Ab,antibody,intraperitoneally,injected,every,week,each,enzyme,linked,immunosorbent,assay,serum,total,cholesterol,triglyceride,Hematoxylin,eosin,CD68,staining,observe,morphological,properties,arterial,plaques,Results,dependent,reduction,response,relation,siHIF,cells,inhibited,reduced,expressions,also,existed,presence,treated,had,increased,atherosclerotic,both,well,reducing,areas,narrowing,wall,thickness,alleviating,lesion,symptoms,some,extent,Conclusion,positive,effects,improving,inhibiting,through

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