The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regul...The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.展开更多
目的分析桃红四物汤通过单磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路对大鼠动脉粥样硬化形成的影响及作用机制。方法选取60只清洁级雄性SD大鼠,其...目的分析桃红四物汤通过单磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路对大鼠动脉粥样硬化形成的影响及作用机制。方法选取60只清洁级雄性SD大鼠,其中10只作为空白组,其余50只采用高脂饮食喂养及动脉内膜损伤方法建立动脉粥样硬化模型,按照随机数表法分为对照组、桃红四物汤低浓度组(L组)、桃红四物汤中浓度组(M组)、桃红四物汤高浓度组(H组)。造模后第9周开始中药干预。空白组与对照组每日予蒸馏水3 mL灌胃,L、M及H组每日分别予相应剂量浓缩至3 mL灌胃。药物干预共8周。观察大鼠下肢动脉粥样硬化斑块程度、AMPK/mTOR信号通路以及血管平滑肌细胞表型转化相关的血管平滑肌激动蛋白(α-smooth muscle actin,α-SMA)、骨桥蛋白(osteopontin,OPN)的差异表达情况。结果与空白组相比,L、M及H组大鼠动脉粥样硬化明显形成,内膜下可见泡沫细胞形成,p-AMPK、OPN在L、M及H组中明显高表达,而mTOR、α-SMA的表达明显下调(P<0.05)。结论桃红四物汤可通过激活AMPK/mTOR信号通路,降低平滑肌细胞收缩表型向合成表型的转化,从而抑制平滑肌细胞的增殖,减缓动脉粥样硬化的进展。展开更多
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
基金supported by grants from Simons Foundation (SFARI 479754),CIHR (PJT-180565)the Scottish Rite Charitable Foundation of Canada (to YL)funding from the Canada Research Chairs program。
文摘The mechanistic target of rapamycin(m TOR) is a serine/threonine kinase that plays a pivotal role in cellular growth, proliferation, survival, and metabolism. In the central nervous system(CNS), the mTOR pathway regulates diverse aspects of neural development and function. Genetic mutations within the m TOR pathway lead to severe neurodevelopmental disorders, collectively known as “mTORopathies”(Crino, 2020). Dysfunctions of m TOR, including both its hyperactivation and hypoactivation, have also been implicated in a wide spectrum of other neurodevelopmental and neurodegenerative conditions, highlighting its importance in CNS health.
文摘目的分析桃红四物汤通过单磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路对大鼠动脉粥样硬化形成的影响及作用机制。方法选取60只清洁级雄性SD大鼠,其中10只作为空白组,其余50只采用高脂饮食喂养及动脉内膜损伤方法建立动脉粥样硬化模型,按照随机数表法分为对照组、桃红四物汤低浓度组(L组)、桃红四物汤中浓度组(M组)、桃红四物汤高浓度组(H组)。造模后第9周开始中药干预。空白组与对照组每日予蒸馏水3 mL灌胃,L、M及H组每日分别予相应剂量浓缩至3 mL灌胃。药物干预共8周。观察大鼠下肢动脉粥样硬化斑块程度、AMPK/mTOR信号通路以及血管平滑肌细胞表型转化相关的血管平滑肌激动蛋白(α-smooth muscle actin,α-SMA)、骨桥蛋白(osteopontin,OPN)的差异表达情况。结果与空白组相比,L、M及H组大鼠动脉粥样硬化明显形成,内膜下可见泡沫细胞形成,p-AMPK、OPN在L、M及H组中明显高表达,而mTOR、α-SMA的表达明显下调(P<0.05)。结论桃红四物汤可通过激活AMPK/mTOR信号通路,降低平滑肌细胞收缩表型向合成表型的转化,从而抑制平滑肌细胞的增殖,减缓动脉粥样硬化的进展。
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.
