多囊卵巢综合征(Polycystic ovary syndrome,PCOS)是一组生殖内分泌代谢紊乱的综合征,临床以稀发排卵、高雄激素体征、胰岛素抵抗为主要特征,其中育龄期发病率高,对女性生育力造成严重不良影响。PCOS的发生发展涉及多种信号通路,腺苷酸...多囊卵巢综合征(Polycystic ovary syndrome,PCOS)是一组生殖内分泌代谢紊乱的综合征,临床以稀发排卵、高雄激素体征、胰岛素抵抗为主要特征,其中育龄期发病率高,对女性生育力造成严重不良影响。PCOS的发生发展涉及多种信号通路,腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)及哺乳动物雷帕霉素靶蛋白(Mammalian target of rapamycin,mTOR)作为细胞能量感受器是其中两个关键靶点。二者在PCOS各个发病部位包括下丘脑-垂体-卵巢轴、子宫内膜、脂肪与骨骼肌中发挥重要的调节作用,通过影响细胞自噬、氧化应激、炎症、线粒体功能、葡萄糖摄取等,促进卵泡的发育和成熟,改善胰岛素抵抗。近年来,中医药因其成分多样、靶点众多等优势广泛应用于临床,研究人员已对PCOS的发病以及中药治疗及改善PCOS的机制进行了大量研究,结果提示AMPK与mTOR相关通路在其中发挥关键作用。通过总结中药干预AMPK与mTOR及其相关通路治疗PCOS的研究结果,为临床治疗及基础研究提供参考。展开更多
Background:Metabolic stress has been proposed to contribute to neuronal damage in glaucoma,but the mechanism driving this response is not understood.The adenosine monophosphate-activated protein kinase(AMPK)is a maste...Background:Metabolic stress has been proposed to contribute to neuronal damage in glaucoma,but the mechanism driving this response is not understood.The adenosine monophosphate-activated protein kinase(AMPK)is a master regulator of energy homeostasis that becomes active at the onset of energy stress.AMPK is a potent inhibitor of the mammalian target of rapamycin complex 1(mTORC1),which we showed is essential for the maintenance of retinal ganglion cell(RGC)dendrites,synapses,and survival.Here,we tested the hypothesis that AMPK is an early mediator of metabolic stress in glaucoma.Methods:Unilateral elevation of intraocular pressure was induced by injection of magnetic microbeads into the anterior chamber of mice expressing yellow fluorescent protein in RGCs.Inhibition of AMPK was achieved by administration of siRNA or compound C.RGC dendritic trees were 3D-reconstructed and analyzed with Imaris(Bitplane),and survival was assessed by counting Brn3a or RBPMS-labeled soma and axons in the optic nerve.RGC function was examined by quantification of anterograde axonal transport after intraocular administration of cholera toxinβ-subunit.Retinas from glaucoma patients were analyzed for expression of active AMPK.Results:Ocular hypertension triggered rapid upregulation of AMPK activity in RGCs concomitant with loss of mTORC1 function.AMPK inhibition with compound C or siRNA effectively restored mTORC1 activity and promoted an increase in total dendritic length,surface and complexity relative to control retinas.Attenuation of AMPK activity led to robust RGC soma and axon survival.For example,95%of RGCs(2,983±258 RGCs/mm2,mean±S.E.M.)survived with compound C compared to 77%in vehicle-treated eyes(2,430±233 RGCs/mm2)(ANOVA,P<0.001)at three weeks after glaucoma induction(n=8-10/group).Importantly,blockade of AMPK activity effectively restored anterograde axonal transport.Lastly,RGC-specific upregulation of AMPK activity was detected in human glaucomatous retinas relative to age-matched controls(n=10/group).Conclusions:Metabolic stress in glaucoma involves AMPK activation and mTORC1 inhibition promoting early RGC dendritic pathology,dysfunction and neurodegeneration.展开更多
Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of ade...Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1(UCP1) and other thermogenic genes in WAT and3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase(AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.展开更多
The AMP-activated protein kinase(AMPK)is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells.While it appears to have evolved in single-celled eukaryotes to regulate energy bala...The AMP-activated protein kinase(AMPK)is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells.While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner,during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level,by responding to hormones that act primarily on the hypothalamus.AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP,and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed.Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans,such as type 2 diabetes,cancer and inflammatory disorders,there has been a major drive to develop pharmacological activators of AMPK.Many such activators have been described,and the various mechanisms by which these activate AMPK will be discussed.A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines.While the mechanism by which most of these activate AMPK has not yet been addressed,I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores,and that many of them will turn out to be inhibitors of mitochondrial function.展开更多
背景:近年来,有研究发现部分中药单体通过激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。目的:综述中药单体调控细胞自噬防治皮瓣坏死的研究进展。方法:分别以“中药、细胞自噬、皮瓣”与“Traditional Chi...背景:近年来,有研究发现部分中药单体通过激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。目的:综述中药单体调控细胞自噬防治皮瓣坏死的研究进展。方法:分别以“中药、细胞自噬、皮瓣”与“Traditional Chinese Medicine (TCM),Autophagy,Skin flaps”为中英文检索词,由第一作者检索2010年1月至2022年10月发表在中国知网与PubMed数据库的相关文献,文献初筛共检索到相关文献196篇,以纳入和排除标准进行筛选,通过阅读文献标题与摘要进行质量评估,最终归纳整理55篇文献进行综述。结果与结论:(1)细胞自噬的调控是由AMPK/mTOR和PI3K/AKT等信号通路介导的,激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。(2)中药单体中的萜类化合物(桦木酸、穿心莲内酯、三七三萜和梓醇)、酚类化合物(白藜芦醇、姜黄素和天麻素)、酚酸类化合物(丹酚酸B)及类固醇类化合物(拟人参皂甙F11)可通过调控相关信号通路激活细胞自噬来缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,促皮瓣存活。(3)文章通过总结中药单体调控细胞自噬防治皮瓣坏死的研究进展,为临床上中药防治皮瓣坏死、促进皮瓣愈合提供参考与理论依据。展开更多
Background Recent studies on bone have shown an endocrine role of the skeleton,which could be impaired in various human diseases,including osteoporosis,obesity,and diabetes-associated bone diseases.As a sensor and reg...Background Recent studies on bone have shown an endocrine role of the skeleton,which could be impaired in various human diseases,including osteoporosis,obesity,and diabetes-associated bone diseases.As a sensor and regulator of energy metabolism,AMP-activated protein kinase （AMPK） may also play an important role in the regulation of bone metabolism.The current study aimed to establish the expression profiles and phosphorylation patterns of AMPK subunits in several mesenchymal cell types.Methods Reverse transcription-polymerase chain reaction （PCR） for relative quantification,real-time PCR for absolute quantification,and Western blotting were used to investigate the gene expression profiles and phosphorylation patterns of AMPK subunits in several mesenchymal cell types,including primary human mesenchymal stem cells （hMSCs） and hFOB,Saos-2,C3H/10T1/2,MC3T3-E1,3T3-L1,and C2C12 cells.Results AMPKα1 and AMPKβ1 mRNAs were abundantly expressed in all cell types.AMPKY1 mRNA was abundantly expressed in C3H/10T1/2,MC3T3-E1,3T3-L1,and C2C12 but not detected in human-derived cell types.AMPKY2 mRNA was mildly expressed in all cell types.AMPKα1 protein was highly expressed in all cell types and AMPKα2 protein was highly expressed only in hFOB and Saos-2 cells.AMPKβ1 protein was abundantly expressed in all cell types except for Saos-2,in which AMPKβ2 protein overwhelmed AMPKβ1 expression.AMPKy1 and AMPKY2 proteins were expressed in C3H/10T1/2,MC3T3-E1,3T3-L1,and C2C12 cells and only AMPKY2 protein was expressed in hMSCs,hFOB and Saos2 cells.AMPKα was phosphorylated at Thr172 and Ser485 and AMPKβ1 was phosphorylated at Ser108 and Ser182 in all cell types with a specific pattern in each cell type.Conclusion The combination of AMPK α,β,and Y subunits and phosphorylation of AMPKα （Thr172 and Ser485） and AMPKβ1 （Ser108 and Ser182） showed a specific pattern in each cell type.展开更多
目的:研究祛湿化瘀方对高脂饮食诱导的大鼠脂肪肝AMPK蛋白活性及其相关脂肪代谢靶蛋白活性的影响,以探讨该方防治实验性脂肪肝的作用机制。方法:采用高脂饲料饮食诱导大鼠脂肪肝模型,造模大鼠给予高脂饮食4周后,按随机数字表随机分为模...目的:研究祛湿化瘀方对高脂饮食诱导的大鼠脂肪肝AMPK蛋白活性及其相关脂肪代谢靶蛋白活性的影响,以探讨该方防治实验性脂肪肝的作用机制。方法:采用高脂饲料饮食诱导大鼠脂肪肝模型,造模大鼠给予高脂饮食4周后,按随机数字表随机分为模型组及祛湿化瘀方组,分别灌胃给予饮用水及中药祛湿化瘀方4周。实验8周末取材后观察:1)肝组织三酰甘油(Triglyceride,TG)、游离脂肪酸(Free Fatty Acid,FFA)含量,2)肝组织病理变化(HE染色、油红染色),3)肝组织腺苷酸活化的蛋白激酶(AMP-Activated K inase,AMPK)及磷酸化AMPK、肝组织总蛋白及核蛋白固醇调节元件结合蛋白-1c(Sterol Regulatory Element Binding Protein-1c、SREBP-1c)、肝组织总蛋白及核蛋白碳水化合物反应元件结合蛋白(Carbohydrate Response Element Binding Protein、ChREBP)含量、肝组织乙酰辅酶A羧化酶(Acety1 Co A Carboxylase,ACCase)及磷酸化ACC蛋白含量,4)肝组织AMPKα1、AMPKα2、SREBP-1、ACCα、SREBP-1c及ChREBP基因表达水平。结果:1)模型组肝组织TG、FFA含量显著升高,肝组织出现明显大泡样脂肪变性;模型组肝组织AMPK蛋白磷酸化水平降低、核蛋白SREBP-1与ChREBP表达增加、ACC蛋白磷酸化水平降低蛋白活性升高。2)祛湿化瘀方组肝组织TG、FFA含量较模型组显著降低,肝组织炎症及脂肪变性程度减轻;祛湿化瘀方能显著升高肝组织AMPK、ACC蛋白磷酸化水平、降低核蛋白SREBP-1及ChREBP含量。结论:祛湿化瘀方通过调节AMPK活性及其相关靶蛋白活性改善高脂饮食诱导的大鼠脂肪肝肝脂肪代谢,这可能是该方有效防治实验性脂肪肝的重要作用机制之一。展开更多
二甲双胍是一种传统的口服降糖药,临床上普遍用于2型糖尿病的治疗。近年来大量流行病学研究报道二甲双胍能够降低2型糖尿病患者的肿瘤发病率,亦有研究发现二甲双胍能在代谢途径、细胞周期、氧化应激、肿瘤干细胞转化等方面通过激活腺苷...二甲双胍是一种传统的口服降糖药,临床上普遍用于2型糖尿病的治疗。近年来大量流行病学研究报道二甲双胍能够降低2型糖尿病患者的肿瘤发病率,亦有研究发现二甲双胍能在代谢途径、细胞周期、氧化应激、肿瘤干细胞转化等方面通过激活腺苷酸活化蛋白激酶(adenosin emonophosphate-activated protein kinase,AMPK)信号通路,从而抑制肿瘤细胞的生长、增殖以及转化。但二甲双胍通过激活AMPK的抗肿瘤机制仍存在着争议,其确切的作用机制有待进一步深入的研究,同时亟需大规模的临床试验来证实。展开更多
文摘多囊卵巢综合征(Polycystic ovary syndrome,PCOS)是一组生殖内分泌代谢紊乱的综合征,临床以稀发排卵、高雄激素体征、胰岛素抵抗为主要特征,其中育龄期发病率高,对女性生育力造成严重不良影响。PCOS的发生发展涉及多种信号通路,腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)及哺乳动物雷帕霉素靶蛋白(Mammalian target of rapamycin,mTOR)作为细胞能量感受器是其中两个关键靶点。二者在PCOS各个发病部位包括下丘脑-垂体-卵巢轴、子宫内膜、脂肪与骨骼肌中发挥重要的调节作用,通过影响细胞自噬、氧化应激、炎症、线粒体功能、葡萄糖摄取等,促进卵泡的发育和成熟,改善胰岛素抵抗。近年来,中医药因其成分多样、靶点众多等优势广泛应用于临床,研究人员已对PCOS的发病以及中药治疗及改善PCOS的机制进行了大量研究,结果提示AMPK与mTOR相关通路在其中发挥关键作用。通过总结中药干预AMPK与mTOR及其相关通路治疗PCOS的研究结果,为临床治疗及基础研究提供参考。
文摘Background:Metabolic stress has been proposed to contribute to neuronal damage in glaucoma,but the mechanism driving this response is not understood.The adenosine monophosphate-activated protein kinase(AMPK)is a master regulator of energy homeostasis that becomes active at the onset of energy stress.AMPK is a potent inhibitor of the mammalian target of rapamycin complex 1(mTORC1),which we showed is essential for the maintenance of retinal ganglion cell(RGC)dendrites,synapses,and survival.Here,we tested the hypothesis that AMPK is an early mediator of metabolic stress in glaucoma.Methods:Unilateral elevation of intraocular pressure was induced by injection of magnetic microbeads into the anterior chamber of mice expressing yellow fluorescent protein in RGCs.Inhibition of AMPK was achieved by administration of siRNA or compound C.RGC dendritic trees were 3D-reconstructed and analyzed with Imaris(Bitplane),and survival was assessed by counting Brn3a or RBPMS-labeled soma and axons in the optic nerve.RGC function was examined by quantification of anterograde axonal transport after intraocular administration of cholera toxinβ-subunit.Retinas from glaucoma patients were analyzed for expression of active AMPK.Results:Ocular hypertension triggered rapid upregulation of AMPK activity in RGCs concomitant with loss of mTORC1 function.AMPK inhibition with compound C or siRNA effectively restored mTORC1 activity and promoted an increase in total dendritic length,surface and complexity relative to control retinas.Attenuation of AMPK activity led to robust RGC soma and axon survival.For example,95%of RGCs(2,983±258 RGCs/mm2,mean±S.E.M.)survived with compound C compared to 77%in vehicle-treated eyes(2,430±233 RGCs/mm2)(ANOVA,P<0.001)at three weeks after glaucoma induction(n=8-10/group).Importantly,blockade of AMPK activity effectively restored anterograde axonal transport.Lastly,RGC-specific upregulation of AMPK activity was detected in human glaucomatous retinas relative to age-matched controls(n=10/group).Conclusions:Metabolic stress in glaucoma involves AMPK activation and mTORC1 inhibition promoting early RGC dendritic pathology,dysfunction and neurodegeneration.
基金supported financially by the National Natural Science Foundation of China (81402983, 81573436)CAMS Innovation Fund for Medical Sciences (CIFMS) 2016-I2M-3–015the National Major Scientific and Technological Special Project for "Significant New Drugs Development" (2015ZX09501005, China)
文摘Obesity is a worldwide epidemic. Promoting browning of white adipose tissue(WAT)contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin(Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Cpn markedly increases the surface temperature around the inguinal WAT and turns the inguinal fat browner. Further investigations show that Cpn induces the development of brown-like adipocytes in inguinal and, to a less degree, epididymal WAT depots. Cpn also increases the expression of uncoupling protein 1(UCP1) and other thermogenic genes in WAT and3T3-L1 differentiated adipocytes, in which AMP-activated protein kinase(AMPK) plays an important role. Our results provide novel insights into the function of Cpn in regulating energy balance, and suggest a potential utility of Cpn in the treatment of obesity.
基金funded by a Senior Investigator Award(No.097726)from the Wellcome Trusta programme grant(No.C37030/A15101)from Cancer Research UK
文摘The AMP-activated protein kinase(AMPK)is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells.While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner,during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level,by responding to hormones that act primarily on the hypothalamus.AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP,and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed.Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans,such as type 2 diabetes,cancer and inflammatory disorders,there has been a major drive to develop pharmacological activators of AMPK.Many such activators have been described,and the various mechanisms by which these activate AMPK will be discussed.A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines.While the mechanism by which most of these activate AMPK has not yet been addressed,I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores,and that many of them will turn out to be inhibitors of mitochondrial function.
文摘背景:近年来,有研究发现部分中药单体通过激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。目的:综述中药单体调控细胞自噬防治皮瓣坏死的研究进展。方法:分别以“中药、细胞自噬、皮瓣”与“Traditional Chinese Medicine (TCM),Autophagy,Skin flaps”为中英文检索词,由第一作者检索2010年1月至2022年10月发表在中国知网与PubMed数据库的相关文献,文献初筛共检索到相关文献196篇,以纳入和排除标准进行筛选,通过阅读文献标题与摘要进行质量评估,最终归纳整理55篇文献进行综述。结果与结论:(1)细胞自噬的调控是由AMPK/mTOR和PI3K/AKT等信号通路介导的,激活细胞自噬可缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,防治皮瓣坏死。(2)中药单体中的萜类化合物(桦木酸、穿心莲内酯、三七三萜和梓醇)、酚类化合物(白藜芦醇、姜黄素和天麻素)、酚酸类化合物(丹酚酸B)及类固醇类化合物(拟人参皂甙F11)可通过调控相关信号通路激活细胞自噬来缓解皮瓣氧化应激与细胞凋亡,促进皮瓣血管再生,促皮瓣存活。(3)文章通过总结中药单体调控细胞自噬防治皮瓣坏死的研究进展,为临床上中药防治皮瓣坏死、促进皮瓣愈合提供参考与理论依据。
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81000778, 81370050, and 81172549） and the Scientific Research and Innovation of Shanghai Municipal Education Commission （No. 11YZ46）.
文摘Background Recent studies on bone have shown an endocrine role of the skeleton,which could be impaired in various human diseases,including osteoporosis,obesity,and diabetes-associated bone diseases.As a sensor and regulator of energy metabolism,AMP-activated protein kinase （AMPK） may also play an important role in the regulation of bone metabolism.The current study aimed to establish the expression profiles and phosphorylation patterns of AMPK subunits in several mesenchymal cell types.Methods Reverse transcription-polymerase chain reaction （PCR） for relative quantification,real-time PCR for absolute quantification,and Western blotting were used to investigate the gene expression profiles and phosphorylation patterns of AMPK subunits in several mesenchymal cell types,including primary human mesenchymal stem cells （hMSCs） and hFOB,Saos-2,C3H/10T1/2,MC3T3-E1,3T3-L1,and C2C12 cells.Results AMPKα1 and AMPKβ1 mRNAs were abundantly expressed in all cell types.AMPKY1 mRNA was abundantly expressed in C3H/10T1/2,MC3T3-E1,3T3-L1,and C2C12 but not detected in human-derived cell types.AMPKY2 mRNA was mildly expressed in all cell types.AMPKα1 protein was highly expressed in all cell types and AMPKα2 protein was highly expressed only in hFOB and Saos-2 cells.AMPKβ1 protein was abundantly expressed in all cell types except for Saos-2,in which AMPKβ2 protein overwhelmed AMPKβ1 expression.AMPKy1 and AMPKY2 proteins were expressed in C3H/10T1/2,MC3T3-E1,3T3-L1,and C2C12 cells and only AMPKY2 protein was expressed in hMSCs,hFOB and Saos2 cells.AMPKα was phosphorylated at Thr172 and Ser485 and AMPKβ1 was phosphorylated at Ser108 and Ser182 in all cell types with a specific pattern in each cell type.Conclusion The combination of AMPK α,β,and Y subunits and phosphorylation of AMPKα （Thr172 and Ser485） and AMPKβ1 （Ser108 and Ser182） showed a specific pattern in each cell type.
文摘目的:研究祛湿化瘀方对高脂饮食诱导的大鼠脂肪肝AMPK蛋白活性及其相关脂肪代谢靶蛋白活性的影响,以探讨该方防治实验性脂肪肝的作用机制。方法:采用高脂饲料饮食诱导大鼠脂肪肝模型,造模大鼠给予高脂饮食4周后,按随机数字表随机分为模型组及祛湿化瘀方组,分别灌胃给予饮用水及中药祛湿化瘀方4周。实验8周末取材后观察:1)肝组织三酰甘油(Triglyceride,TG)、游离脂肪酸(Free Fatty Acid,FFA)含量,2)肝组织病理变化(HE染色、油红染色),3)肝组织腺苷酸活化的蛋白激酶(AMP-Activated K inase,AMPK)及磷酸化AMPK、肝组织总蛋白及核蛋白固醇调节元件结合蛋白-1c(Sterol Regulatory Element Binding Protein-1c、SREBP-1c)、肝组织总蛋白及核蛋白碳水化合物反应元件结合蛋白(Carbohydrate Response Element Binding Protein、ChREBP)含量、肝组织乙酰辅酶A羧化酶(Acety1 Co A Carboxylase,ACCase)及磷酸化ACC蛋白含量,4)肝组织AMPKα1、AMPKα2、SREBP-1、ACCα、SREBP-1c及ChREBP基因表达水平。结果:1)模型组肝组织TG、FFA含量显著升高,肝组织出现明显大泡样脂肪变性;模型组肝组织AMPK蛋白磷酸化水平降低、核蛋白SREBP-1与ChREBP表达增加、ACC蛋白磷酸化水平降低蛋白活性升高。2)祛湿化瘀方组肝组织TG、FFA含量较模型组显著降低,肝组织炎症及脂肪变性程度减轻;祛湿化瘀方能显著升高肝组织AMPK、ACC蛋白磷酸化水平、降低核蛋白SREBP-1及ChREBP含量。结论:祛湿化瘀方通过调节AMPK活性及其相关靶蛋白活性改善高脂饮食诱导的大鼠脂肪肝肝脂肪代谢,这可能是该方有效防治实验性脂肪肝的重要作用机制之一。
文摘二甲双胍是一种传统的口服降糖药,临床上普遍用于2型糖尿病的治疗。近年来大量流行病学研究报道二甲双胍能够降低2型糖尿病患者的肿瘤发病率,亦有研究发现二甲双胍能在代谢途径、细胞周期、氧化应激、肿瘤干细胞转化等方面通过激活腺苷酸活化蛋白激酶(adenosin emonophosphate-activated protein kinase,AMPK)信号通路,从而抑制肿瘤细胞的生长、增殖以及转化。但二甲双胍通过激活AMPK的抗肿瘤机制仍存在着争议,其确切的作用机制有待进一步深入的研究,同时亟需大规模的临床试验来证实。
