Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,...Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,and the rats received oral CSⅣor atorvastatin.The body weight,organ weights,food intake,calorie intake,lipid parameters,3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)/mevalonate ratio,collagen,free fatty acid,cardiac parameters,apolipoprotein(A and B),antioxidant parameters,inflammatory cytokines,and inflammatory parameters were assessed.The mRNA expressions of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),IL-6,IL-17,PI3K,AKT,and mTOR were estimated.Results:CSⅣsignificantly modulated food intake,body weight,organ weight(liver,kidney,and heart),and calories(P<0.05).Total cholesterol,triglycerides,very low-density lipoprotein cholesterol,low-density lipoprotein cholesterol,cardiovascular risk index-1,and cardiovascular risk index-2 were decreased,while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSⅣgroup(P<0.05).Besides,CSⅣsignificantly restored the level of HMG-CoA/mevalonate ratio,collagen,free fatty acid,cardiac parameters(creatinine kinase-MB,lactate dehydrogenase,cTnT,cTnI),apolipoprotein(apolipoprotein A and apolipoprotein B),antioxidant parameters(MDA,CAT,GPx,GSH,SOD),inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10),inflammatory parameters(COX-2,TGF-β,NF-κB),intercellular adhesion molecule-1,vascular cell adhesion molecule-1,and monocyte chemoattractant protein-1.CSⅣalso decreased the mRNA expression of IL-1β,TNF-α,IL-6,IL-17,PI3K,AKT,and mTOR.Conclusions:This study showed the anti-atherosclerosis effect of CSⅣagainst high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.展开更多
目的分析沉默分化簇(CD)147对非小细胞肺癌(NSCLC)细胞生物学特征及上皮间质转化(EMT)的影响,并探究可能的相关分子机制。方法回顾性收集2023年8月~2024年3月空军军医大学唐都医院收治的30例NSCLC患者癌灶组织及癌旁正常组织样本,从中...目的分析沉默分化簇(CD)147对非小细胞肺癌(NSCLC)细胞生物学特征及上皮间质转化(EMT)的影响,并探究可能的相关分子机制。方法回顾性收集2023年8月~2024年3月空军军医大学唐都医院收治的30例NSCLC患者癌灶组织及癌旁正常组织样本,从中科院细胞库购买人正常肺上皮细胞BEAS-2B及NSCLC细胞系A549、NCI-H460、NCI-H1299,采用实时荧光定量PCR(qRT-PCR)法检测NSCLC癌灶组织和癌旁正常组织,以及各细胞系中CD147 mRNA表达水平。将NCI-H460细胞分为control组、si-NC组、si-CD147组、SC-79组及si-CD147+SC-79组,通过CCK-8法、Transwell法及流式细胞仪检测敲低CD147对NSCLC细胞增殖、迁移、凋亡的影响。蛋白免疫印迹(Western blot)检测EMT相关标志物神经钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)、上皮钙黏附蛋白(E-cadherin)及锌指转录因子(Slug)、扭曲蛋白(Twist)表达,以及磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路相关蛋白表达。结果NSCLC组织中CD147 mRNA(1.64±0.25)表达水平明显高于癌旁正常组织(0.43±0.06),差异具有统计学意义(t=8.152,P<0.05)。NSCLC细胞中CD147 mRNA表达水平较人正常肺上皮细胞明显升高(1.24±0.13、3.31±0.37、2.16±0.29 vs 0.35±0.04),差异具有统计学意义(F=80.516,P<0.05)。与control组相比,si-CD147组细胞增殖率(53.74%±4.07%vs 78.92%±6.23%)、迁移率(19.57%±2.69%vs 37.24%±3.12%)明显降低,细胞凋亡率(39.04%±2.74%vs 16.14%±2.14%)明显升高(t=5.548、7.068、12.036),N-cadherin(0.41±0.02 vs 1.01±0.02)、Vimentin(0.36±0.04 vs 1.02±0.04)蛋白表达降低,E-cadherin(1.85±0.14 vs 0.98±0.02)蛋白表达升高,Slug(0.49±0.03 vs 1.02±0.03)和Twist(0.53±0.05 vs 1.03±0.04)蛋白水平明显抑制(t=12.766~36.742),p-PI3K(0.42±0.03 vs 1.01±0.03)、p-AKT(0.45±0.03 vs 1.01±0.02)和p-mTOR(0.38±0.02 vs 0.99±0.02)蛋白表达水平明显降低(t=8.377、7.286、9.694),差异具有统计学意义(均P<0.05)。与SC-79组相比,si-CD147+SC-79组p-PI3K、p-AKT、p-mTOR蛋白表达明显升高(t=11.075、14.573、13.666),促进细胞增殖及迁移、降低细胞凋亡、促进EMT过程(t=2.834~11.396),差异具有统计学意义(均P<0.05);SC-79可逆转敲低CD147对PI3K/AKT/mTOR通路的影响(t=11.643、8.848、10.965)和PI3K/AKT/mTOR通路相关蛋白的表达(t=2.595~14.476),差异具有统计学意义(均P<0.05)。结论CD147高表达可通过PI3K/AKT/mTOR通路诱导EMT过程,促进肿瘤细胞的增殖及迁移,抑制细胞凋亡,参与NSCLC的发生发展。展开更多
基金funded by the Yancheng Municipal Health Commission 2024 Medical Research Project(YK2024166).
文摘Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,and the rats received oral CSⅣor atorvastatin.The body weight,organ weights,food intake,calorie intake,lipid parameters,3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)/mevalonate ratio,collagen,free fatty acid,cardiac parameters,apolipoprotein(A and B),antioxidant parameters,inflammatory cytokines,and inflammatory parameters were assessed.The mRNA expressions of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),IL-6,IL-17,PI3K,AKT,and mTOR were estimated.Results:CSⅣsignificantly modulated food intake,body weight,organ weight(liver,kidney,and heart),and calories(P<0.05).Total cholesterol,triglycerides,very low-density lipoprotein cholesterol,low-density lipoprotein cholesterol,cardiovascular risk index-1,and cardiovascular risk index-2 were decreased,while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSⅣgroup(P<0.05).Besides,CSⅣsignificantly restored the level of HMG-CoA/mevalonate ratio,collagen,free fatty acid,cardiac parameters(creatinine kinase-MB,lactate dehydrogenase,cTnT,cTnI),apolipoprotein(apolipoprotein A and apolipoprotein B),antioxidant parameters(MDA,CAT,GPx,GSH,SOD),inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10),inflammatory parameters(COX-2,TGF-β,NF-κB),intercellular adhesion molecule-1,vascular cell adhesion molecule-1,and monocyte chemoattractant protein-1.CSⅣalso decreased the mRNA expression of IL-1β,TNF-α,IL-6,IL-17,PI3K,AKT,and mTOR.Conclusions:This study showed the anti-atherosclerosis effect of CSⅣagainst high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.
文摘目的分析沉默分化簇(CD)147对非小细胞肺癌(NSCLC)细胞生物学特征及上皮间质转化(EMT)的影响,并探究可能的相关分子机制。方法回顾性收集2023年8月~2024年3月空军军医大学唐都医院收治的30例NSCLC患者癌灶组织及癌旁正常组织样本,从中科院细胞库购买人正常肺上皮细胞BEAS-2B及NSCLC细胞系A549、NCI-H460、NCI-H1299,采用实时荧光定量PCR(qRT-PCR)法检测NSCLC癌灶组织和癌旁正常组织,以及各细胞系中CD147 mRNA表达水平。将NCI-H460细胞分为control组、si-NC组、si-CD147组、SC-79组及si-CD147+SC-79组,通过CCK-8法、Transwell法及流式细胞仪检测敲低CD147对NSCLC细胞增殖、迁移、凋亡的影响。蛋白免疫印迹(Western blot)检测EMT相关标志物神经钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)、上皮钙黏附蛋白(E-cadherin)及锌指转录因子(Slug)、扭曲蛋白(Twist)表达,以及磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路相关蛋白表达。结果NSCLC组织中CD147 mRNA(1.64±0.25)表达水平明显高于癌旁正常组织(0.43±0.06),差异具有统计学意义(t=8.152,P<0.05)。NSCLC细胞中CD147 mRNA表达水平较人正常肺上皮细胞明显升高(1.24±0.13、3.31±0.37、2.16±0.29 vs 0.35±0.04),差异具有统计学意义(F=80.516,P<0.05)。与control组相比,si-CD147组细胞增殖率(53.74%±4.07%vs 78.92%±6.23%)、迁移率(19.57%±2.69%vs 37.24%±3.12%)明显降低,细胞凋亡率(39.04%±2.74%vs 16.14%±2.14%)明显升高(t=5.548、7.068、12.036),N-cadherin(0.41±0.02 vs 1.01±0.02)、Vimentin(0.36±0.04 vs 1.02±0.04)蛋白表达降低,E-cadherin(1.85±0.14 vs 0.98±0.02)蛋白表达升高,Slug(0.49±0.03 vs 1.02±0.03)和Twist(0.53±0.05 vs 1.03±0.04)蛋白水平明显抑制(t=12.766~36.742),p-PI3K(0.42±0.03 vs 1.01±0.03)、p-AKT(0.45±0.03 vs 1.01±0.02)和p-mTOR(0.38±0.02 vs 0.99±0.02)蛋白表达水平明显降低(t=8.377、7.286、9.694),差异具有统计学意义(均P<0.05)。与SC-79组相比,si-CD147+SC-79组p-PI3K、p-AKT、p-mTOR蛋白表达明显升高(t=11.075、14.573、13.666),促进细胞增殖及迁移、降低细胞凋亡、促进EMT过程(t=2.834~11.396),差异具有统计学意义(均P<0.05);SC-79可逆转敲低CD147对PI3K/AKT/mTOR通路的影响(t=11.643、8.848、10.965)和PI3K/AKT/mTOR通路相关蛋白的表达(t=2.595~14.476),差异具有统计学意义(均P<0.05)。结论CD147高表达可通过PI3K/AKT/mTOR通路诱导EMT过程,促进肿瘤细胞的增殖及迁移,抑制细胞凋亡,参与NSCLC的发生发展。
