OBJECTIVE:To investigate the mechanism of Dan Ze mixture(丹泽合剂,DZM)in the treatment of lipotoxic cardiomyopathy.METHODS:Ultra-performance liquid chromatography tandem mass spectrometry was employed to characterize ...OBJECTIVE:To investigate the mechanism of Dan Ze mixture(丹泽合剂,DZM)in the treatment of lipotoxic cardiomyopathy.METHODS:Ultra-performance liquid chromatography tandem mass spectrometry was employed to characterize the serum migration constituents of DZM.A lipotoxic cardiomyopathy rat model was established through high-fat diet and intervened by different doses of DZM.The cardiac function was assessed using echocardiography,and hematoxylin and eosin,oil red O,and Masson staining were conducted to evaluate morphological changes,lipid accumulation,and fibrosis in myocardial tissue.Serum myocardial enzyme activity,lipid levels,and lipid content of myocardial tissue were measured,while fluorescent staining and colorimetry were used to assess oxidation levels in myocardial tissue.Mitochondrial membrane potential was detected by 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanineiodide(JC-1).Transmission electron microscopy was employed to observe ultrastructure and mitochondrial structure changes in myocardial tissue.Fluorescence double staining and colocalization were utilized to observe the binding of autophagosomes and mitochondria,while immunohistochemical staining was used to detect the expression of mitophagy-related proteins.Terminal deoxynucleoitidyl transferase mediated nick end labeling staining was employed for the identification of apoptosis in myocardial tissue,while quantitative real-time reverse transcriptase polymerase chain reaction(q RT-PCR)and Western blot were utilized for the detection of apoptosis,B-cell lymphoma-2 adenovirus E1B 19 k Da-interacting protein 3(BNIP3)/mitophagy signaling pathway-related genes and proteins.In palmitic acid-induced Rat H9C2 cardiomyocytes(H9c2)cells,various cellular parameters including cell viability,lactate dehydrogenase release,apoptosis rate,oxidative stress level,mitochondrial structure and function,and mitophagy level were assessed after the treatment of DZM drug-containing serum for a duration of 24 h.The cellular expressions of BNIP3/mitophagy signaling pathway relevant genes and proteins were further evaluated using q RT-PCR and Western blot techniques.RESULTS:A total of 295 prototypes(e.g.,phenolic acids,quinones,terpenoids)were identified in serum of rats after oral administration of DZM.In vivo,DZM therapy has been shown to effectively enhance cardiac function,mitigate high-fat diet-induced myocardial structural damage and lipid accumulation.Furthermore,DZM has demonstrated the ability to reduce lipid levels,attenuate cell apoptosis,combat oxidative stress,enhance mitochondrial structure and function,and activate the BNIP3/mitophagy signaling pathway.Furthermore,the silencing of BNIP3 has been shown to exacerbate palmitic acid-induced damages in H9c2 cells,while inhibiting the BNIP3/mitophagy signaling pathway can mitigate the inhibitory effects of DZM on palmitic acidinduced apoptosis,lipid deposition and oxidative stress.CONCLUSION:This study presents preliminary evidence for the therapeutic efficacy of DZM on lipotoxic cardiomyopathy through the activating BNIP3/mitophagy signaling pathway.展开更多
新型制冷剂R1234ze(E)(trans-1,3,3,3-tetrafluoropropene)因较低的GWP而被广泛关注,有望在热泵中作为R134a的替代品。本文对R1234ze(E)在内径为8 mm水平管内流动沸腾过程中摩擦压降特性进行实验研究,并在相同实验工况下与R134a进行对...新型制冷剂R1234ze(E)(trans-1,3,3,3-tetrafluoropropene)因较低的GWP而被广泛关注,有望在热泵中作为R134a的替代品。本文对R1234ze(E)在内径为8 mm水平管内流动沸腾过程中摩擦压降特性进行实验研究,并在相同实验工况下与R134a进行对比。实验研究的流动沸腾换热的饱和温度为10℃,热流密度为5.0 k W/m^2和10.0 k W/m^2,质流密度范围为300~500 kg/(m^2·s),并分析质流密度、热流密度对R1234ze(E)和R134a饱和流动沸腾过程中摩擦压降的影响。结果表明,在相同工况下R1234ze(E)的流动沸腾过程的摩擦压降略大于R134a,如质流密度为500 kg/(m^2·s)时,R1234ze(E)的平均摩擦压降值比R134a大8.4%左右。最后,将实验结果同四种摩擦压降经验关联式进行比较分析。展开更多
为了解新型环保工质R1234ze(E)微小通道内的冷凝换热及阻力特性,提出采用VOF(volume of fluid)模型对R1234ze(E)和R134a(Tsat=40℃)在水平微细圆管(Dh=1mm)内的冷凝过程进行数值模拟研究,探讨质量流量、干度以及物性对管内冷凝换热和阻...为了解新型环保工质R1234ze(E)微小通道内的冷凝换热及阻力特性,提出采用VOF(volume of fluid)模型对R1234ze(E)和R134a(Tsat=40℃)在水平微细圆管(Dh=1mm)内的冷凝过程进行数值模拟研究,探讨质量流量、干度以及物性对管内冷凝换热和阻力性能的影响。结果表明,R1234ze(E)和R134a的换热系数和压降都随质量流速和干度的增大而增大。相同情况下,R1234ze(E)换热系数小于R134a,但压降大于R134a。R1234ze(E)的液膜厚度平均要比R134a薄15.7%。当气液两相都为湍流,有效热导率对不同工质在水平圆管内的冷凝换热性能有重要影响。R1234ze(E)在管内的液膜分布特性整体上和R134a相似。现有的关联式对R1234ze(E)的压降都存在一定的低估,平均绝对误差都在30%左右。展开更多
基金Scientific Research Project of Hebei Province Administration of Traditional Chinese Medicine:to Explore the Protective Effect and Mechanism of Zexie Decoction on Lipotoxic Cardiomyopathy based on the p-mitogen-activated protein kinases/Peroxisome proliferator-activated receptorγcoactivator 1-alpha(p MAPK/PGC-1α)Signaling Pathway(No.2022096)Medical Science Research Project of Hebei Province:the Effect of 23-acetyl Alismol-B on Mitochondrial Function in Palmitic Acid-induced H9c2 Cells Was Investigated based on the Ca2+-Cyclic Adenosine Monophosphate(c AMP)-Response Element Binding Protein/c AMP Response Element(CREB/CRE)-PGC-1αSignaling Pathway(No.20221490)+1 种基金Hebei province natural science fund project:Study on the Mechanism of Danshen Zexie Decoction in Activating Nuclear Factor Erythroid 2-related Factor 2 Signaling Pathway to Trigger 0mi/Htr A2,Restoring Autophagic Flux and Enhancing Metabolism-Related Fatty Liver Disease(No.H2023423064)Hebei graduate student innovation ability funding training project:to Investigate the Protective Effects and Underlying Mechanisms of Zexie Decoction on Lipotoxic Cardiomyopathy,with A Focus on the PGC-1a Signaling Pathway(No.CXZZBS2022096)。
文摘OBJECTIVE:To investigate the mechanism of Dan Ze mixture(丹泽合剂,DZM)in the treatment of lipotoxic cardiomyopathy.METHODS:Ultra-performance liquid chromatography tandem mass spectrometry was employed to characterize the serum migration constituents of DZM.A lipotoxic cardiomyopathy rat model was established through high-fat diet and intervened by different doses of DZM.The cardiac function was assessed using echocardiography,and hematoxylin and eosin,oil red O,and Masson staining were conducted to evaluate morphological changes,lipid accumulation,and fibrosis in myocardial tissue.Serum myocardial enzyme activity,lipid levels,and lipid content of myocardial tissue were measured,while fluorescent staining and colorimetry were used to assess oxidation levels in myocardial tissue.Mitochondrial membrane potential was detected by 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanineiodide(JC-1).Transmission electron microscopy was employed to observe ultrastructure and mitochondrial structure changes in myocardial tissue.Fluorescence double staining and colocalization were utilized to observe the binding of autophagosomes and mitochondria,while immunohistochemical staining was used to detect the expression of mitophagy-related proteins.Terminal deoxynucleoitidyl transferase mediated nick end labeling staining was employed for the identification of apoptosis in myocardial tissue,while quantitative real-time reverse transcriptase polymerase chain reaction(q RT-PCR)and Western blot were utilized for the detection of apoptosis,B-cell lymphoma-2 adenovirus E1B 19 k Da-interacting protein 3(BNIP3)/mitophagy signaling pathway-related genes and proteins.In palmitic acid-induced Rat H9C2 cardiomyocytes(H9c2)cells,various cellular parameters including cell viability,lactate dehydrogenase release,apoptosis rate,oxidative stress level,mitochondrial structure and function,and mitophagy level were assessed after the treatment of DZM drug-containing serum for a duration of 24 h.The cellular expressions of BNIP3/mitophagy signaling pathway relevant genes and proteins were further evaluated using q RT-PCR and Western blot techniques.RESULTS:A total of 295 prototypes(e.g.,phenolic acids,quinones,terpenoids)were identified in serum of rats after oral administration of DZM.In vivo,DZM therapy has been shown to effectively enhance cardiac function,mitigate high-fat diet-induced myocardial structural damage and lipid accumulation.Furthermore,DZM has demonstrated the ability to reduce lipid levels,attenuate cell apoptosis,combat oxidative stress,enhance mitochondrial structure and function,and activate the BNIP3/mitophagy signaling pathway.Furthermore,the silencing of BNIP3 has been shown to exacerbate palmitic acid-induced damages in H9c2 cells,while inhibiting the BNIP3/mitophagy signaling pathway can mitigate the inhibitory effects of DZM on palmitic acidinduced apoptosis,lipid deposition and oxidative stress.CONCLUSION:This study presents preliminary evidence for the therapeutic efficacy of DZM on lipotoxic cardiomyopathy through the activating BNIP3/mitophagy signaling pathway.
文摘新型制冷剂R1234ze(E)(trans-1,3,3,3-tetrafluoropropene)因较低的GWP而被广泛关注,有望在热泵中作为R134a的替代品。本文对R1234ze(E)在内径为8 mm水平管内流动沸腾过程中摩擦压降特性进行实验研究,并在相同实验工况下与R134a进行对比。实验研究的流动沸腾换热的饱和温度为10℃,热流密度为5.0 k W/m^2和10.0 k W/m^2,质流密度范围为300~500 kg/(m^2·s),并分析质流密度、热流密度对R1234ze(E)和R134a饱和流动沸腾过程中摩擦压降的影响。结果表明,在相同工况下R1234ze(E)的流动沸腾过程的摩擦压降略大于R134a,如质流密度为500 kg/(m^2·s)时,R1234ze(E)的平均摩擦压降值比R134a大8.4%左右。最后,将实验结果同四种摩擦压降经验关联式进行比较分析。
文摘为了解新型环保工质R1234ze(E)微小通道内的冷凝换热及阻力特性,提出采用VOF(volume of fluid)模型对R1234ze(E)和R134a(Tsat=40℃)在水平微细圆管(Dh=1mm)内的冷凝过程进行数值模拟研究,探讨质量流量、干度以及物性对管内冷凝换热和阻力性能的影响。结果表明,R1234ze(E)和R134a的换热系数和压降都随质量流速和干度的增大而增大。相同情况下,R1234ze(E)换热系数小于R134a,但压降大于R134a。R1234ze(E)的液膜厚度平均要比R134a薄15.7%。当气液两相都为湍流,有效热导率对不同工质在水平圆管内的冷凝换热性能有重要影响。R1234ze(E)在管内的液膜分布特性整体上和R134a相似。现有的关联式对R1234ze(E)的压降都存在一定的低估,平均绝对误差都在30%左右。
