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
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。
