OBJECTIVE: To evaluate the efficacy of Shoushen granule, prepared with four Chinese medicinals, on the targeted regulation of adenosine triphosphate binding cassette transporter A1(ABCA1) through proprotein convertase...OBJECTIVE: To evaluate the efficacy of Shoushen granule, prepared with four Chinese medicinals, on the targeted regulation of adenosine triphosphate binding cassette transporter A1(ABCA1) through proprotein convertase subtilisin/kexin type 9(PCSK9) and toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB) signaling pathway to affect atherosclerosis(AS) in ApoE-knockout(ApoE-/-) mice.METHODS: ApoE-/-mice fed with a high-fat diet were used for AS modeling and divided into Model,Shoushen, and Atorvastatin groups. C57 BL/6 J mice at the same age and background strain were included in the Control group. Western blot and immunohistochemistry were used to measure ABCA1, PCSK9, TLR4, and NF-κB protein expression in mouse aortas. Enzyme-linked immuno sorbent assay was used to measure mouse serum tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), monocyte chemoattractant protein 1(MCP-1), and intercellular cell adhesion molecule-1(ICAM-1) expression. Serum lipid profiles and histopathology were also assessed. Shoushen granule were composed of Heshouwu(Radix Polygoni Multiflori) 15 g, Gouqizi(Fructus Lycii) 15 g, Sheng shanzha(Raw Fructus Crataegus Pinnatifidae) 10 g, and Sanqi(Radix Notoginseng) 3 g.RESULTS: ApoE-/-mice fed with a high-fat diet had notable AS lesions, with reduced ABCA1 and IL-10 levels, elevated PCSK9, TLR4, NF-κB, TNF-α, MCP-1,and ICAM-1 expression, and increased total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) contents. With drug interventions, the areas of AS plaques were significantly reduced,the ABCA1 and IL-10 levels were increase, while the PCSK9, TLR4, NF-κB, TC, and LDL-C contents,and the TNF-α, MCP-1, and ICAM-1 expression were reduced.CONCLUSION: Shoushen granule effectively interfered with AS development by antagonizing the expression of key factors of the PCSK9 and TLR4/NF-κB signaling pathway to upregulate ABCA1 expression.展开更多
OBJECTIVE:To study the effect of Bushen Jiangzhi formula(BSJZF)on atherosclerosis(AS)in apolipoprotein E knockout(apoE^-/-)mice and the underlying mechanism.METHODS:We used a high fat diet to induce AS in apoE^-/- mic...OBJECTIVE:To study the effect of Bushen Jiangzhi formula(BSJZF)on atherosclerosis(AS)in apolipoprotein E knockout(apoE^-/-)mice and the underlying mechanism.METHODS:We used a high fat diet to induce AS in apoE^-/- mice.The mice were randomly divided into four groups:model,BSJZF,atorvastatin,and 3-methyladenine groups.Syngeneic C57BL/6 mice of the same age were used for the control group.Autophagosomes in the aorta were examined by transmission electron microscopy.Morphology,lipid accumulation,and collagen deposition in the aorta were examined by hematoxylin and eosin,Oil Red O,and Masson's staining,respectively.Serum levels of tumor necrosis factor alpha(TNF-α),interferon gamma(IFN-γ),and interleukin 10(IL-10)were measured by enzyme-linked immunoassays.Protein expression of microtubule-associated protein light chain 3(LC3),Beclin 1,and p62 in the aorta were examined by Western blot analyses.RESULTS:ApoE^-/- mice fed a high fat diet exhibited AS symptoms including less autophagosomes in the aorta,higher serum levels of TNF-α,IFN-γ,and p62,and lower serum levels of IL-10,LC3,and Beclin 1.Treatment with BSJZF significantly reduced the area of the aortic plaque,decreased expression of TNF-α,IFN-γ,and p62,and increased expression of IL-10,LC3,and Beclin 1.CONCLUSION:Our findings suggest that BSJZF promotes autophagy and reduces inflammation by regulating the expression of autophagy-related proteins LC3,Beclin 1,and p62,thereby effectively treating AS.展开更多
基金Supported by the National Natural Science Foundation of China(The Role of TLR4/MyD88/NF-κB Signal Transduction Pathway and Expression of miRNA-146a in Atherosclerosis and the Intervention Mechanism of Shen Invigorating Compounds,No.81202731Bushen Jiangzhi Recipe Protects Against Atherosclerosis via miR-27a-mediated PCSK9/ABCA1 Pathway,No.81873348)+2 种基金the Shanghai Natural Science Found(Inhibitory Mechanism of Chinese Herbal Compound,Shoushen Granule,for Invigorating Kidney in ApoE-/-Atherosclerosis Mouse Model by mir-19b Target Regulating ABCA1,No.16ZR1433900)the Shanghai Municipal Commission of Health and Family Planning Found(Effect of Kidney Invigoration and Lipid Intervention on the Atherosclerosis in ApoE-knockout Mice Based on mT OR signaling pathway of Autophagy System,No.201640217)Shanghai University of Traditional Chinese Medicine graduate"innovation ability training"special research projects(Mechanism of Bushen Jiangzhi Recipe Regulating TLR4/NF-κB Signaling Pathway Mediated by CD36 Through PCSK9 Targeted Regulation of apoE-/-mice Atherosclerosis,No.Y201858)
文摘OBJECTIVE: To evaluate the efficacy of Shoushen granule, prepared with four Chinese medicinals, on the targeted regulation of adenosine triphosphate binding cassette transporter A1(ABCA1) through proprotein convertase subtilisin/kexin type 9(PCSK9) and toll-like receptor 4(TLR4)/nuclear factor kappa-B(NF-κB) signaling pathway to affect atherosclerosis(AS) in ApoE-knockout(ApoE-/-) mice.METHODS: ApoE-/-mice fed with a high-fat diet were used for AS modeling and divided into Model,Shoushen, and Atorvastatin groups. C57 BL/6 J mice at the same age and background strain were included in the Control group. Western blot and immunohistochemistry were used to measure ABCA1, PCSK9, TLR4, and NF-κB protein expression in mouse aortas. Enzyme-linked immuno sorbent assay was used to measure mouse serum tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), monocyte chemoattractant protein 1(MCP-1), and intercellular cell adhesion molecule-1(ICAM-1) expression. Serum lipid profiles and histopathology were also assessed. Shoushen granule were composed of Heshouwu(Radix Polygoni Multiflori) 15 g, Gouqizi(Fructus Lycii) 15 g, Sheng shanzha(Raw Fructus Crataegus Pinnatifidae) 10 g, and Sanqi(Radix Notoginseng) 3 g.RESULTS: ApoE-/-mice fed with a high-fat diet had notable AS lesions, with reduced ABCA1 and IL-10 levels, elevated PCSK9, TLR4, NF-κB, TNF-α, MCP-1,and ICAM-1 expression, and increased total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) contents. With drug interventions, the areas of AS plaques were significantly reduced,the ABCA1 and IL-10 levels were increase, while the PCSK9, TLR4, NF-κB, TC, and LDL-C contents,and the TNF-α, MCP-1, and ICAM-1 expression were reduced.CONCLUSION: Shoushen granule effectively interfered with AS development by antagonizing the expression of key factors of the PCSK9 and TLR4/NF-κB signaling pathway to upregulate ABCA1 expression.
基金grants from the National Natural Science Foundation of China(Bushen Jiangzhi formula Protects Against Atherosclerosis via miR-27a-mediated PCSK9/ABCA1 Pathway,No.81873348)National Traditional Chinese Medicine Innovation Talent Training Project[Letter(2019)No.128]Shanghai Health and Family Planning Commission Fund(Effect of Bushen Jiangzhi Formula Intervention on the Atherosclerosis in ApoE^-/-knockout Mice Based on mTOR signaling pathway of Autophagy System,No.201640217)。
文摘OBJECTIVE:To study the effect of Bushen Jiangzhi formula(BSJZF)on atherosclerosis(AS)in apolipoprotein E knockout(apoE^-/-)mice and the underlying mechanism.METHODS:We used a high fat diet to induce AS in apoE^-/- mice.The mice were randomly divided into four groups:model,BSJZF,atorvastatin,and 3-methyladenine groups.Syngeneic C57BL/6 mice of the same age were used for the control group.Autophagosomes in the aorta were examined by transmission electron microscopy.Morphology,lipid accumulation,and collagen deposition in the aorta were examined by hematoxylin and eosin,Oil Red O,and Masson's staining,respectively.Serum levels of tumor necrosis factor alpha(TNF-α),interferon gamma(IFN-γ),and interleukin 10(IL-10)were measured by enzyme-linked immunoassays.Protein expression of microtubule-associated protein light chain 3(LC3),Beclin 1,and p62 in the aorta were examined by Western blot analyses.RESULTS:ApoE^-/- mice fed a high fat diet exhibited AS symptoms including less autophagosomes in the aorta,higher serum levels of TNF-α,IFN-γ,and p62,and lower serum levels of IL-10,LC3,and Beclin 1.Treatment with BSJZF significantly reduced the area of the aortic plaque,decreased expression of TNF-α,IFN-γ,and p62,and increased expression of IL-10,LC3,and Beclin 1.CONCLUSION:Our findings suggest that BSJZF promotes autophagy and reduces inflammation by regulating the expression of autophagy-related proteins LC3,Beclin 1,and p62,thereby effectively treating AS.
