目的研究外周血CD4^(+)CD28^(null)T细胞、肿瘤坏死因子受体超家族成员4(OX40)、4-1BB变化与糖尿病患者动脉粥样硬化(AS)进展的关联性。方法选取2型糖尿病(T2DM)患者120例,根据是否合并AS分为DM-AS组和DM组,比较两组外周血CD4^(+)CD28^(...目的研究外周血CD4^(+)CD28^(null)T细胞、肿瘤坏死因子受体超家族成员4(OX40)、4-1BB变化与糖尿病患者动脉粥样硬化(AS)进展的关联性。方法选取2型糖尿病(T2DM)患者120例,根据是否合并AS分为DM-AS组和DM组,比较两组外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率变化,并根据颈动脉狭窄程度分为轻度AS组(狭窄≤50%)、中度AS组(狭窄51%~69%)及重度AS组(狭窄≥70%),分析CD4^(+)CD28^(null)T细胞、OX40、4-1BB变化与AS进展的关联性。结果120例患者中,DM-AS组有76例,占63.33%;与DM组相比,DM-AS组的DM病程、收缩压、餐后2 h血糖(2 h PG)、糖化血红蛋白、载脂蛋白B、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平及CD4^(+)CD28^(null)T细胞亚群比率、OX40阳性比率、4-1BB阳性比率较高,载脂蛋白A1水平较低,差异均有统计学意义(t分别=2.57、2.49、2.78、2.19、3.12、2.94、4.31、5.97、16.91、11.47、-2.52,P均<0.05);CD4^(+)CD28^(null)T细胞、OX40、4-1BB联合诊断DM-AS的曲线下面积(AUC)为0.96。DM-AS组76例中,其中轻度AS组37例、中度AS组29例、重度AS组10例。AS程度与CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均呈正相关(r分别=0.24、0.48、0.38,P均<0.05)。结论DM-AS患者的外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均明显升高,对DM-AS具有诊断价值,与AS进展呈正相关。展开更多
Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential...Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.展开更多
文摘目的研究外周血CD4^(+)CD28^(null)T细胞、肿瘤坏死因子受体超家族成员4(OX40)、4-1BB变化与糖尿病患者动脉粥样硬化(AS)进展的关联性。方法选取2型糖尿病(T2DM)患者120例,根据是否合并AS分为DM-AS组和DM组,比较两组外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率变化,并根据颈动脉狭窄程度分为轻度AS组(狭窄≤50%)、中度AS组(狭窄51%~69%)及重度AS组(狭窄≥70%),分析CD4^(+)CD28^(null)T细胞、OX40、4-1BB变化与AS进展的关联性。结果120例患者中,DM-AS组有76例,占63.33%;与DM组相比,DM-AS组的DM病程、收缩压、餐后2 h血糖(2 h PG)、糖化血红蛋白、载脂蛋白B、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平及CD4^(+)CD28^(null)T细胞亚群比率、OX40阳性比率、4-1BB阳性比率较高,载脂蛋白A1水平较低,差异均有统计学意义(t分别=2.57、2.49、2.78、2.19、3.12、2.94、4.31、5.97、16.91、11.47、-2.52,P均<0.05);CD4^(+)CD28^(null)T细胞、OX40、4-1BB联合诊断DM-AS的曲线下面积(AUC)为0.96。DM-AS组76例中,其中轻度AS组37例、中度AS组29例、重度AS组10例。AS程度与CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均呈正相关(r分别=0.24、0.48、0.38,P均<0.05)。结论DM-AS患者的外周血CD4^(+)CD28^(null)T细胞亚群比率及OX40、4-1BB阳性比率均明显升高,对DM-AS具有诊断价值,与AS进展呈正相关。
基金Natural Science Foundation of Zhejiang Province(grant number LY20H290005)Key Research and Development Program of Zhejiang Province(grant number 2020C03119)+2 种基金National Natural Science Foundation of China(grant numbers 81673706,81973579,82174150)Science and Technology Program of Zhejiang Traditional Chinese Medicine(grant number 2018ZY005)TCM science and Technology Foundation Project of Zhejiang Province(grant number 2023ZL411).
文摘Background:Atherosclerosis(AS)is a chronic progressive inflammatory disease,and plaque stability plays a critical role in preventing acute events.Tanyu Tongzhi formula(TTF),a traditional Chinese medicine,has potential therapeutic effects on AS.Methods:We used an AS animal model to examine the effects of TTF on atherosclerotic plaque vulnerability and CD40^(+)monocyte differentiation.AS plaque area,collagen content,and lipid area were assessed using histological staining.AS plaque-related biomarkers(monocyte chemoattractant protein 1(MCP-1),monocyte plus macrophage(MOMA-2),von Willebrand factor(vWF),CD31,and alpha-smooth muscle actin(α-SMA))were detected using immunohistochemistry.Inflammatory cytokines were determined using enzyme-linked immunosorbent assay.CD40 mRNA expression was detected by real-time quantitative PCR.CD40^(+)monocyte differentiation was evaluated by flow cytometry analysis in ApoE-/-mice and peripheral blood mononuclear cells(PBMCs).AMPK/NF-κB signaling pathways-related protein expression was investigated through western blotting.Results:TTF treatment reduced AS plaque area,collagen content,and lipid area in AS model mice.Levels of MCP-1,MOMA-2,vWF,and CD31 were decreased,whileα-SMA level was increased by TTF in model mice.TTF reduced inflammatory cytokines levels,including tumor necrosis factor receptor-α(TNF-α),high-sensitivity C-reactive protein(hs-CRP),and interleukin-6(IL-6).TTF inhibited CD40^(+)monocyte differentiation and decreased the number of CD40^(+)/CD40-and Ly6C^(+)/Ly6C-cells and M1/M2 ratio in AS model mice and human PBMCs.Additionally,TTF modulated the AMPK/NF-κB signaling pathway in human PBMCs.Conclusion:TTF attenuates atherosclerotic plaque vulnerability by inhibiting CD40^(+)monocyte differentiation,possibly through the regulation of the AMPK/NF-κB signaling pathway.These findings suggest that TTF could be a potential therapeutic agent for preventing plaque rupture and subsequent cardiovascular events in patients with AS.
